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Lithium attenuated the behavioral despair induced by acute neurogenic stress through blockade of opioid receptors in mice
Biomedicine & Pharmacotherapy 83 (2016) 1006–1015
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Original article
Lithium attenuated the behavioral despair induced by acute neurogenic stress through blockade of opioid receptors in mice Pegah Khalooa,b,1, Banafshe Sadeghia,b,1, Sattar Ostadhadia,c , Abbas Norouzi-Javidanc , Arya Haj-Mirzaiana,b , Samira Zolfagharied , Ahmad-Reza Dehpoura,b,* a
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran d Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran b c
A R T I C L E I N F O
Article history: Received 25 June 2016 Received in revised form 4 August 2016 Accepted 7 August 2016 Keywords: Lithium Opioid Neurogenic stress Forced swimming test Mice
A B S T R A C T
Major depressive disorder is disease with high rate of morbidity and mortality. Stressful events lead to depression and they can be used as a model of depression in rodents. In this study we aimed to investigate whether lithium modifies the stressed-induced depression through blockade of opioid receptors in mice. We used foot shock stress as stressor and forced swimming test (FST), tail suspension test (TST) and open field test (OFT) to evaluation the behavioral responses in mice. We also used naltrexone hydrochloride (as opioid receptor antagonist), and morphine (as opioid receptor agonist). Our results displayed that footshock stress significantly increased the immobility time in TST and FST but it could not change the locomotor behavior in OFT. When we combined the low concentrations of lithium and naltrexone a significant reduction in immobility time was seen in the FST and TST in comparison with control footshock stressed group administered saline only. Despite the fact that our data showed low concentrations of lithium, when administered independently did not significantly affect the immobility time. Also our data indicated that concurrent administration of lithium and naltrexone had no effect on open field test. Further we demonstrated that simultaneous administration of morphine and lithium reverses the antidepressant like effect of active doses of lithium. Our data acclaimed that we lithium can augment stressed-induced depression and opioid pathways are involved in this action. ã 2016 Published by Elsevier Masson SAS.
1. Introduction Major depressive disorder (MDD) is a disease with a high rate of mortality and morbidity [1]. Patients with MDD also suffer from other medical disorders including coronary artery disease, diabetes and cancer due to their depression [2]. Exposure to acute or chronic stress can lead to major depressive disorders [3]. It has been said that there is a relation between occurrence of depression and emotional stress in individuals [4], Therefore acute or chronic stress induction in rodents are widely used as a model of depression [5] Several studies support the antidepressant effect of lithium especially in treatment resistant depression [6,7] Even some studies suggest that lithium may augment the anti-suicidal effects
* Corresponding author at: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran. E-mail address: [email protected] (A.-R. Dehpour). 1 Both authors have contributed equally to this project. http://dx.doi.org/10.1016/j.biopha.2016.08.015 0753-3322/ã 2016 Published by Elsevier Masson SAS.
of other antidepressant drugs and it can reduce the risk of complete suicide in adult patients with unipolar depression [6]. Though the effects of lithium on patients with bipolar mood disorder are more clear [8]. Moreover it has been said that lithium alters stress-induced changes in mouse hippocampus [9]. Lithium treatment may also modifies long term effect of stress on neuropeptide Y, This protein is suggested to play a role in development of depression [10]. However the definite mechanism for antidepressant effect of lithium is still unknown. There are many hypotheses. There are some evidence that indicate an association between opioid analgesic exposure and symptoms of depression [11]. An association between duration of opioid analgesic use and the risk of development of depression has also been discussed [11]. The change in mu-opioid receptors also results in normalizing stress-induced depression in rodents [5]. For"show_abs example it has been suggested that opioid receptors alone or in combination with N-methyl-D-aspartate have a role in protective effect of fluoxetine against the depressive-like behavior induced by acute stress [12].
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In addition studies suggest that lithium is effective on opioid receptors in rat brain [13]. For example mu-opioid receptor expression reveals an increase by chronic lithium treatment [14]. It has been shown that the motivational effect of lithium is a result of its influence on opioid receptors in the central nervous system [15]. The aim of this study is to investigate whether opioid systems are involved in the protective effect of lithium treatment against behavioral despair induced by acute stress. To examine this hypothesis we used foot shock stress as a stressor and also forced swimming test, tail suspension test and open field test to evaluate animal behavioral responses to stress.
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2.5. Open-field test (OFT) Locomotion behavior of animals in response to drugs was evaluated by an Open-field test [23]. Immediately after 30 min foot-shock stress, mice were gently removed from the box and were separately placed in open field apparatus. The open-field apparatus consisted of a wooden box (60 cm 50 cm 40 cm) which was divided into 12 squares. Each mouse was placed gently in the center of the field and behavior was recorded by counting the number of squares crossing for 6 min. After each test, the surface of the apparatus was cleaned with solution of 70% ethanol to hide animal clues. Each mouse was used in only one experiment [24].
2. Material and methods 2.6. Tail suspension test (TST) 2.1. Animals Male adult NMRI (Naval Medical Research Institute) mice (Pasture institute of Iran) weighting 21–30 g were used throughout the study. The animals were housed in groups of six to seven in Plexiglas boxes (25 25 15) under standard conditions (12-h light-dark cycle, temperature 24 2 C). Animals had free access to food and water aside from the period they were removed from cages to be tested. All behavioral experiments were performed between 8:00 a.m. and 14:00 p.m. Also, each experimental group contained 6–8 animals. All procedures in this study were carried out in accordance with institutional guidelines for animal care and use (Department of Pharmacology, School of Medicine, TUMS). 2.2. Drugs and treatment The following drugs were used in this study: Naltrexone hydrochloride, Lithium chloride and Morphine Sulfate. All drugs were dissolved in physiological saline .All drugs in different doses were prepared in constant volume of 1 mg/kg immediately before the experiments. All injections were administered intraperitoneally (i.p.) but Morphine Sulfate was administered subcutaneous (S.C). 2.3. Foot-shock stress Stress was induced by a picket box (30 30 40 cm3 high) with a steel-rod floor (29 parallel rods, 0.3 cm in diameter set one cm apart). Inevitable foot-shock (3-mA scrambled shock stimulus, 50Hz) was delivered through a scrambler to the grid ground [16,17]. Animals were exposed to intermittent foot-shock for thirty minutes (Five-s pulses delivered each 30 s for 30 min). Animals were allowed to adopt with the equipment for thirty minutes just before stress induction [12,18]. Right away after this point mice were placed in the open field equipment. On the day of the experiments, right away after FSS, each mouse was mildly removed from this box and evaluated by one of the behavioral tests. It was not possible to perform more than one behavioral test in each animal, since the behavioral tasks are supposed to be conducted immediately after stress exposure. 2.4. Forced swimming test (FST) Immediately after 30 min foot-shock stress, mice were gently removed from the box and were separately placed in an open glass cylinder (diameter: 10 cm, height: 25 cm) filled with 19 cm of water at 23 1 C and allowed to swim for 6 min [19–21]. The method of Porsolt et al. was used for evaluating depression in rodents [22]. Immobility behavior was considered when the animal was without motion except keeping the head above the water for survive. The immobility time was recorded during the last 4 min of the test by two expert raters.
The tail suspension test was conducted as previously described by Steru et al. [25]. Immediately after 30 min foot-shock stress, mice were gently removed from the box and were separately evaluated in TST. Animals were individually suspended by the tail 50 cm above the table top by using an adhesive tape placed 1 cm from the tip. Test lasted for 6 min and mice were considered to be immobile when they were motionless or hung passively by 2 blind observers to result [26,27]. 2.7. Experimental procedure Initially, we determined the effect of acute FSS on the mice immobility time in the FST and TST and also the locomotor activity in the OFT. In the next experiment we acquired the effective and subeffective doses of lithium in behavioral tests. For this purpose, animals (with/without experience to FSS) were injected by lithium (1 and 5 and 10 mg/kg) [8,28,29].immediately before exposure to intermittent foot-shock stress and 30 min [8,28,29].before beginning of behavioral tests (locomotor behavior in OFT and the time of immobility in FST or TST). Saline (5 mL/kg) was administrated into control animals to exclude the effect of saline injection on the animals’ behavior. Next, we tried to examine the probable involvement of opioid system in this effects of lithium. So, subeffective dose of naltrexone (0.3 mg/kg) [12,18,30] was coinjected with the subeffective dose of lithium in stressed/nonstressed mice on FST, TST, or OFT. Also, subeffective doses of opioid receptor agonists morphine (1 mg/kg) was applied in our subsequent test, with the effective dose of lithium. Morphine Sulfate was injected immediately before exposure to intermittent foot-shock stress and 30 min before behavioral tests beginning [12,30]. 2.8. Statistical analysis Statistical analyses were carried out using GraphPad Prism 5 software (San Diego, CA, USA). The results are presented as mean + S.E.M. One-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test was carried out to evaluation of dose-related effects of lithium on immobility time, locomotor activity. Two-way ANOVA followed by Bonferroni test was used to analyze the other results. The analysis method applied in each part of the experiment is stated in the Section 3 and “Fig. captions”. Data are expressed as mean + S.E.M. P values less than 0.05 were considered statistically significant. 3. Results 3.1. Effect of acute FSS on the animals behavior in the behavioral tests Fig. 1 shows changes in motor activity and immobility time in mice response to foot-shock exposure in the acute foot-shock stress in acute stress experiment. Depressive effect of foot-shock
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Fig. 1. Effect of acute foot-shock stress (FSS) on behavioral tests. Effect of acute FSS on duration of immobility in forced swimming test (FST) (A) and tail suspension test (TST) (B), and number of crossing in open field test (OFT) (C). Acute-FSS animals were exposed to prolonged, intermittent foot-shock for 30 min and then were immediately evaluated in behavioral tests (D). Values are expressed as the mean SEM; **p < 0.01 vs. control group.
stress was determined in the FST (Fig. 1A) and TST (Fig. 1B). In the OFT (Fig. 1C) no significant changes were observed (p > 0.05). 3.1. Effect of lithium on depressive-like behaviors induced by acute FSS Antidepressant-like effects of Lithium (1, 5, 10 mg/kg i.p.) administered 30 min before FST and TST are shown in Fig. 2. In nonstressed condition, these doses did not have effects on nonstressed mice compared to saline-administered mice in both FST (Fig. 2A) and TST (Fig. 2C). In other hand lithium reversed immobility time induced by foot-shock stress at dose of 5 mg/kg (p 0 < 0.01) and 10 mg/kg (p 0 < 0.001) despite 1 mg/kg did not show antidepressant-like effect in the FST (Fig. 2B). Also acute administration of lithium at dose of 10 mg/kg (p 0 < 0.01) reversed the behavioral despair induced by acute electric shock stress in the TST (Fig. 2D). Fig. 3 shows either in stressed and non-stressed mice, lithium at the administered doses mentioned above did not remarkably changed locomotor activity in the open-field test(p > 0.05). 3.2. Effect of opioid receptors in the antidepressant-like effect of lithium in stressed animals Fig. 4 shows that naltrexone (0.3 mg/kg) did not reduce immobility time in non-stressed mice in both FST (Fig. 4A) and TST (Fig. 4C), neither did in acutely stressed animals in FST (Fig. 4B) and TST (Fig. 4D). In stressed condition, the co-administration of sub-effective doses of lithium (1 mg/kg) and Naltrexone (0.3 mg/ kg) significantly reduced the immobility time in FST (p < 0.001) and TST (p < 0.01) in comparison with control foot-shock stressed group (Fig. 4B and D) while concurrent administration of
naltrexone and lithium did not have effect on open-field test (Fig. 5A and B). Fig. 6 shows that morphine (1 mg/kg) injection did not affect the immobility time in non-stressed and stressed situations (p > 0.05, Fig. 6A–D), but co-administration of an effective dose of lithium (10 mg/kg) with morphine (1 mg/kg) significantly reversed the anti-immobility effect of lithium in acute-FSS group in both FST (p < 0.01, Fig. 6B) and TST (p < 0.01, Fig. 6D), while this treatment did not alter the immobility of non-stressed animals in FST and TST (p > 0.05, Fig. 6A and C). These treatments did not display any significant alterations in the locomotor behaviors (p > 0.05, Fig. 7A and B) of both non-stressed and stressed animals in the OFT. 4. Discussion In current report, we have revealed that induction of acute stress display depressant effect and significantly amplifies the immobility time period in the mice FST and TST. [31]. Previous investigations displayed that uncontrollable shock produces a behavioral deficit and numerous acute stress procedures are accepted as animal paradigms of depressive, though in these models, the time range for determining the behavioral alterations relative to stress is short compared with the long-lasting property of the human disorders[31]. In accordance with previous reports, we presented that acute FSS produced depressive-like behaviors in mice [12,18,30,32]. Also it was showed that the rats immobility period in FST was augmented by acute but not chronic restraint stress, which was then inhibited by naloxone as opioid receptor antagonist [33]. Anisman et al. have presented that acute FSS as an acute neurogenic stressor could stimulate distinct molecular
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Fig. 2. Effect of lithium on behavioral tests. Effect of acute administration of lithium on duration of immobility of non-stressed (NS) and stressed (FSS) mice in forced swimming test (FST) (A, B) and tail suspension test (TST) (C, D) .Lithium at doses of 1, 5 and 10 mg/kg adminestrated 30 min before FST or TST (E). Values are expressed as the mean SEM; ***p < 0.00,1 **p < 0.01 vs. saline-treated group. FSS, foot-shock stress.
Fig. 3. Effect of lithium on behavioral tests. Effect of acute administration of lithium on number of crossing of non-stressed (NS) (A) and stressed (FSS) (B) mice in open field test (OFT). Lithium at doses of 1, 5 and 10 mg/kg administrated 30 min before OFT (E).FSS, foot-shock stress.
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Fig. 4. Effect of treatment with naltrexone (NTX) and its combination with lithium. Effect of administration of NTX (0.3 mg/kg) and its combination with lithium (1 mg/kg) on duration of immobility of non-stressed (NS) and stressed (FSS) mice in forced swimming test (FST) (A, B) and tail suspension test (TST) (C, D). Lithium and/or NTX administrated 30 min before FST or TST(E). Values are expressed as the mean SEM; ***p < 0.001 and **p < 0.01 vs. saline-treated group. FSS, foot-shock stress.
pathways and behavioral effects which are connected to the depression in rodents [34]. In current report behavioral tests including FST and TST, which are well known screening methods for agents with antidepressant effectiveness, were applied in the investigations. Numerous animal paradigms for depression are being applied, FST and TST are the most widely used screening test for antidepressant property in rodents [22,25,35]. The immobile performance reveals behavioral despair which is a disappointment to persevere in escape-directed behavior after stress [35,36]. Meaningful decrease in the time of immobility in these paradigms
after treatment is reflected as a probable antidepressant-like effectiveness of the treatment. Although the FST and TST are quite tried and trusted, false negative consequences might be acquired in sedation and sickness circumstances and also false positive outcomes are sometimes detected with agents which have stimulant effects. Consequently, the locomotor activity is normally assessed in each investigational group to exclude the potential effects of situations and treatments on animals’ locomotor behavior [35,37,38]. The results we obtained from this report appears not to be related with motoric alterations, since animals in
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Fig. 5. Effect of administration of NTX (0.3 mg/kg) and its combination with lithium (1 mg/kg) on number of crossing of non-stressed (NS) (A) and stressed (FSS) (B) mice in open field test (OFT). Lithium and/or NTX administrated 30 min before FST or TST (E). FSS, foot-shock stress.
different groups did not display any significant variations in ambulation in the OFT. Also in present study we evaluated the effect of lithium on depression that induced by acute FSS. Our results showed that the stress-induced immobility in mice is inhibited by acute injection of lithium, in doses tend to be subeffective in none-stressed mice. Lithium is one of these drugs that decrease the immobility time of mice in FST and TST [8]. but the response varies in different strains of mouse [39]. Lithium is the drug of choice for the of mania treatment and bipolar affective disorders prophylaxis, but its molecular mechanisms of action stay poorly recognized [40,41]. Numerous reports also have stated that acute lithium administration decreases immobility time in mice [42,43]. Interestingly, lithium administration also equivalents the property of antidepressants on learned helplessness [44] and immobilization stress in rats [45]. However the definite mechanism for antidepressant effect of lithium is still unknown, there are many hypotheses. One that has been suggested is an enhancement of serotonergic transmission [46]. NMDA receptors signaling [28] and nitric oxide involvement are other hypothesis about lithium mechanisms [8]. Some studies have also demonstrated the role of a-amino-3-hydroxy-5-methyl4isoxazolepropionic acid (AMPA) receptors [47]. Moreover studies have suggested an interaction between lithium and opioid receptors [48]. It has been said the influence of lithium on the treatment of affective illness shares certain actions on opioid receptors in the brain [13]. So in the next step we have assessed the possible involvement of opioid system in lithium inhibitory effect on depressant-like behavior induced by FSS, since opioid tone increases during stress
[49]. In this regards, subeffective doses of opioid receptor antagonist was coadministered with the subeffective dose of lithium in stressed/non-stressed animals. In the present study when we combined the low concentrations of lithium and naltrexone, a significant reduction in immobility time was seen in the FST and TST in comparison with control group. Further we demonstrated that simultaneous administration of morphine and lithium reverses the antidepressant like effect of effective doses of lithium in stressed-mice. Stressful conditions change CNS functions by altering numerous neurotransmitters, endocrine and neuroendocrine systems, mainly monoamines, steroids and neurosteroids [50,51]. The expression and release [52,53] of endogenous opioids in brain enhances subsequent stress experience unconnected to the nature of the stressor. Endogenous opioids display their effects by acting on delta (DOR), kappa (KOR) and mu (MOR) receptors, each with their distinct cellular reactions. Some preceding reports have specified that opioid agonists induce an antidepressant-like effect [54,55]. It was displayed that activation of DOR receptor by met-enkephalin produce antidepressant-like effect in rodents [56,57], however, dynorphin, which stimulates KOR, probably induces depressive like effects [58,59]. Previous studies have revealed that the stimulation of the opioid pathway is involved in the mechanisms underlying the effect of antidepressants [60–63]. Furthermore, the opioid system is also participated in the mechanisms of action of agents such as adenosine [64], folic acid [65] and agmatine [66] that induced an antidepressant-like effects in the FST. These informations showed that the antidepressant effect of these agents was mainly mediated by MOR and DOR stimulation and an inhibition of KOR.
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It has been revealed that opioid receptors differentially and diFig. 6. Effect of treatment with morphine (MOR) and its combination with lithium. Effect of administration of MOR (1 mg/kg) and its combination with lithium (10 mg/kg) on s- duration of immobility of non-stressed (NS) and stressed (FSS) mice in forced swimming test (FST) (A, B) and tail suspension test (TST) (C, D). Lithium and/or MOR t- administrated 30 min before FST or TST (E). Values are expressed as the mean SEM; ***p < 0.001 and **p < 0.01 vs. saline-treated group. #p < 0.05 and ##p < 0.01 vs. lithium i- treated group. FSS, foot-shock stress. nctly involve in the behavioral reactions. Numerous reports have antagonists or by ablation of the genes encoding KORs [72,73, displayed that administration of DOR agonists produced an 75–79]. antidepressant-like effects in FST [67–69]. Equally, injection of The results of our previous report [30], display that inhibition of MOR agonists has been stated to decrease the depressive-like opioid receptors by non-selective antagonist, naltrexone which behaviors in some reports [70,71]. In contrast, KOR agonists blocks all the subtypes of opioid receptors, inhibited the administration has been exposed to induce depressive-like effects immobility time enhancement produced by foot shock stress. in the FST [58]. Also, KOR antagonists have an antidepressant-like There were numerous evidence demonstrating the effects of property in rodents after administration [72,73]. antidepressant on opioid system [63,80,81] and the involvement of Stress stimulates the release of dynorphin, which activates opioids in the pathophysiology of depression. But there were no KORs in the central nervous systems [73–75]. Evidence indicated reports to demonstrate the participation of opioid system in that the acute outcomes of stress are triggered, at least in part, by mediating the antidepressant-like effect of lithium in an animal dynorphin-related KOR stimulation [76]. It was showed that the model of depression. prodepressive-like effects of stress in rodents are reduced by KOR
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Fig. 7. Effect of administration of MOR (1 mg/kg) and its combination with lithium (1 mg/kg) on number of crossing of non-stressed (NS) (A) and stressed (FSS) (B) mice in open field test (OFT). Lithium and/or MOR administrated 30 min before OFT (C). FSS, foot-shock stress.
Numerous reports have also revealed the communication between the lithium and the opioid system. For instance, lithium can decrease morphine tolerance and dependence [82,83], and prevent modulatory properties of morphine on pentylenetetrazole-induced seizure in mice [84]. Furthermore, acute and chronic injection of lithium to rodents may increase or decrease opioidinduced analgesia [85–89], and enhance sensitivity to naloxone as opioid receptor antagonist [90]. In fact, the stated interruption of opioid receptor activity by lithium may suggest possible profits in definite clinical conditions. It has been displayed that lithium produces a reduction in the level of dynorphin (endogenous ligand for KOR) concentration in rat brain [91] . So this is hypothesis that lithium antidepressant effect in stressed-mice is mediated, at least in part, by inhibition of release of dynorphin and finally inhibition of KOR pathway. But there are no studies on the interaction of antidepressant effect of lithium with these subtypes of opioid receptors on FST or TST, neither about the interaction of specific agonists and antagonists of these subtypes with the antidepressant action of lithium in FSS. The present report does not include data on what opioid receptor subtypes including mu, kappa, and delta, participate the antidepressant effect of lithium, so additional experiments are necessary. In conclusion, our results acclaimed that antidepressant-like effect of lithium is opioid mediated. For the first time we showed that lithium attenuate the stress- induced depression in mice and this action is mediated through the opioid pathway. Even so, further studies are necessary to discover the benefits of clinically applied opioid antagonists beside standard antidepressants. References [1] M. Salehi-Sadaghiani, M. Javadi-Paydar, M.H. Gharedaghi, A. Zandieh, P. Heydarpour, Y. Yousefzadeh-Fard, A.R. Dehpour, NMDA receptor involvement in antidepressant-like effect of pioglitazone in the forced swimming test in mice, Psychopharmacology (Berl.) 223 (3) (2012) 345–355.
[2] A.S. Heller, Cortical-subcortical interactions in depression: from animal models to human psychopathology, Front. Syst. Neurosci. 10 (2016) 20. [3] F. Chaouloff, A. Hemar, O. Manzoni, Acute stress facilitates hippocampal CA1 metabotropic glutamate receptor-dependent long-term depression, J. Neurosci. 27 (27) (2007) 7130–7135. [4] Y.K. Kim, N.H. Cha, Correlations among occupational stress, fatigue, and depression in call center employees in Seoul, J. Phys. Ther. Sci. 27 (10) (2015) 3191–3194. [5] F.R. Wang, M.Q. Qiao, L. Xue, S. Wei, Possible involvement of micro opioid receptor in the antidepressant-like effect of Shuyu formula in restraint stressinduced depression-like rats, Evid. Based Complement. Altern. Med. 2015 (2015) 452412. [6] A. Cipriani, F. Girlanda, E. Agrimi, A. Barichello, R. Beneduce, I. Bighelli, G. Bisoffi, A. Bisogno, P. Bortolaso, M. Boso, C. Calandra, L. Cascone, C. Corbascio, V.F. Parise, F. Gardellin, D. Gennaro, B. Hanife, C. Lintas, M. Lorusso, C. Luchetta, C. Lucii, F. Cernuto, F. Tozzi, A. Marsilio, F. Maio, C. Mattei, D. Moretti, M.G. Appino, M. Nose, G. Occhionero, D. Papanti, D. Pecile, M. Purgato, D. Prestia, F. Restaino, T. Sciarma, A. Ruberto, S. Strizzolo, S. Tamborini, O. Todarello, S. Ziero, S. Zotos, C. Barbui, Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial, BMC Psychiatry 13 (2013) 212. [7] T. Bschor, M. Adli, C. Baethge, U. Eichmann, M. Ising, M. Uhr, S. Modell, H. Kunzel, B. Muller-Oerlinghausen, M. Bauer, Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression, Neuropsychopharmacology 27 (3) (2002) 470–478. [8] M. Ghasemi, H. Sadeghipour, A. Mosleh, H.R. Sadeghipour, A.R. Mani, A.R. Dehpour, Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test, Eur. Neuropsychopharmacol. 18 (5) (2008) 323–332. [9] S. Yoshida, M. Maeda, S. Kaku, H. Ikeya, K. Yamada, S. Nakaike, Lithium inhibits stress-induced changes in tau phosphorylation in the mouse hippocampus, J. Neural Transm. (Vienna) 113 (11) (2006) 1803–1814. [10] H. Husum, A.A. Mathe, Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes, Neuropsychopharmacology 27 (5) (2002) 756–764. [11] J.F. Scherrer, D.M. Svrakic, K.E. Freedland, T. Chrusciel, S. Balasubramanian, K.K. Bucholz, E.V. Lawler, P.J. Lustman, Prescription opioid analgesics increase the risk of depression, J. Gen. Intern. Med. 29 (3) (2014) 491–499. [12] A. Haj-Mirzaian, N. Kordjazy, S. Ostadhadi, S. Amiri, A. Haj-Mirzaian, A. Dehpour, Fluoxetine reverses the behavioral despair induced by neurogenic stress in mice: role of N-methyl-d-aspartate and opioid receptors, Can. J. Physiol. Pharmacol. 94 (6) (2016) 599–612. [13] K. Stengaard-Pedersen, M. Schou, Opioid peptides and receptors in relation to affective illness. Effects of desipramine and lithium on opioid receptors in rat brain, Acta Pharmacol. Toxicol. (Copenh.) 56 (Suppl. 1) (1985) 170–179.
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P. Khaloo et al. / Biomedicine & Pharmacotherapy 83 (2016) 1006–1015
[14] M.R. Zarrindast, A. Lahmi, S. Ahamadi, Possible involvement of mu-opioid receptors in effect of lithium on inhibitory avoidance response in mice, J. Psychopharmacol. 22 (8) (2008) 865–871. [15] T.S. Shippenberg, M.J. Millan, R.F. Mucha, A. Herz, Involvement of betaendorphin and mu-opioid receptors in mediating the aversive effect of lithium in the rat, Eur. J. Pharmacol. 154 (2) (1988) 135–144. [16] J.W. Lewis, J.T. Cannon, J.C. Liebeskind, Opioid and nonopioid mechanisms of stress analgesia, Science 208 (4444) (1980) 623–625. [17] J.T. Madden, H. Akil, R.L. Patrick, J.D. Barchas, Stress-induced parallel changes in central opioid levels and pain responsiveness in the rat, Nature 265 (5592) (1977) 358–360. [18] S. Ostadhadi, A. Haj-Mirzaian, V. Nikoui, N. Kordjazy, A.R. Dehpour, Involvement of opioid system in antidepressant-like effect of the cannabinoid CB1 receptor inverse agonist AM-251 after physical stress in mice, Clin. Exp. Pharmacol. Physiol. 43 (2) (2016) 203–212. [19] S. Ostadhadi, M.I. Khan, A. Norouzi-Javidan, M. Chamanara, F. Jazaeri, S. Zolfaghari, A.-R. Dehpour, Involvement of NMDA receptors and l-arginine/ nitric oxide/cyclic guanosine monophosphate pathway in the antidepressantlike effects of topiramate in mice forced swimming test, Brain Res. Bull. 122 (2016) 62–70. [20] M.I. Khan, S. Ostadhadi, S. Zolfaghari, S.E. Mehr, G. Hassanzadeh, A.-R. Dehpour, The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test, Neurosci. Lett. 612 (2016) 52–61. [21] S. Ostadhadi, M.I. Khan, A. Norouzi-Javidan, A.-R. Dehpour, Antidepressant effect of pramipexole in mice forced swimming test: a cross talk between dopamine receptor and NMDA/nitric oxide/cGMP pathway, Biomed. Pharmacother. 81 (2016) 295–304. [22] R. Porsolt, A. Bertin, M. Jalfre, Behavioral despair in mice: a primary screening test for antidepressants, Arch. Int. Pharm. Thér. 229 (2) (1977) 327–336. [23] S. Ostadhadi, M. Ahangari, V. Nikoui, A. Norouzi-Javidan, S. Zolfaghari, F. Jazaeri, M. Chamanara, R. Akbarian, A.-R. Dehpour, Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test, Biomed. Pharmacother. 82 (2016) 713–721. [24] S. Ostadhadi, N. Kordjazy, A. Haj-Mirzaian, S. Ameli, G. Akhlaghipour, A. Dehpour, Involvement of NO/cGMP pathway in the antidepressant-like effect of gabapentin in mouse forced swimming test, Naunyn-Schmiedeberg’s Arch. Pharmacol. 389 (4) (2016) 393–402. [25] L. Steru, R. Chermat, B. Thierry, P. Simon, The tail suspension test: a new method for screening antidepressants in mice, Psychopharmacology (Berl.) 85 (3) (1985) 367–370. [26] N. Kordjazy, A. Haj-Mirzaian, S. Amiri, S. Ostadhadi, H. Amini-khoei, A.R. Dehpour, Involvement of N-methyl-D-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test, Pharmacol. Biochem. Behav. 141 (2016) 1–9. [27] A. Haj-Mirzaian, N. Kordjazy, S. Amiri, A. Haj-Mirzaian, H. Amini-khoei, S. Ostadhadi, A. Dehpour, Involvement of nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tropisetron and ondansetron in mice forced swimming test and tail suspension test, Eur. J. Pharmacol. 780 (2016) 71–81. [28] M. Ghasemi, M. Raza, A.R. Dehpour, NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test, J. Psychopharmacol. 24 (4) (2010) 585–594. [29] A. Bahremand, S.E. Nasrabady, P. Ziai, R. Rahimian, T. Hedayat, B. Payandemehr, A.R. Dehpour, Involvement of nitric oxide-cGMP pathway in the anticonvulsant effects of lithium chloride on PTZ-induced seizure in mice, Epilepsy Res. 89 (2–3) (2010) 295–302. [30] A. Haj-Mirzaian, S. Ostadhadi, N. Kordjazy, A.R. Dehpour, S. Ejtemaei Mehr, Opioid/NMDA receptors blockade reverses the depressant-like behavior of foot shock stress in the mouse forced swimming test, Eur. J. Pharmacol. 735 (2014) 26–31. [31] H.H. Van Dijken, J.A. Van Der Heyden, J. Mos, F.J. Tilders, Inescapable footshocks induce progressive and long-lasting behavioural changes in male rats, Physiol. Behav. 51 (4) (1992) 787–794. [32] J.M. Weiss, P.A. Goodman, B.G. Losito, S. Corrigan, J.M. Charry, W.H. Bailey, Behavioral depression produced by an uncontrollable stressor: relationship to norepinephrine, dopamine, and serotonin levels in various regions of rat brain, Brain Res. Rev. 3 (2) (1981) 167–205. [33] L. Cancela, S. Rossi, V. Molina, Effect of different restraint schedules on the immobility in the forced swim test: modulation by an opiate mechanism, Brain Res. Bull. 26 (5) (1991) 671–675. [34] H. Anisman, S. Hayley, O. Kelly, T. Borowski, Z. Merali, Psychogenic, neurogenic, and systemic stressor effects on plasma corticosterone and behavior: mouse strain-dependent outcomes, Behav. Neurosci. 115 (2) (2001) 443. [35] J.F. Cryan, A. Markou, I. Lucki, Assessing antidepressant activity in rodents: recent developments and future needs, Trends Pharmacol. Sci. 23 (5) (2002) 238–245. [36] A. Haj-Mirzaian, N. Kordjazy, A. Haj-Mirzaian, S. Ostadhadi, M. Ghasemi, S. Amiri, M. Faizi, A. Dehpour, Evidence for the involvement of NMDA receptors in the antidepressant-like effect of nicotine in mouse forced swimming and tail suspension tests, Psychopharmacology 232 (19) (2015) 3551–3561. [37] N. Kordjazy, A. Haj-Mirzaian, S. Amiri, S. Ostadhadi, M. Kordjazy, M. Sharifzadeh, A.R. Dehpour, Elevated level of nitric oxide mediates the anti-
[38]
[39]
[40]
[41] [42] [43]
[44] [45]
[46] [47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
[57]
[58]
[59]
[60]
[61]
[62]
[63]
[64]
depressant effect of rubidium chloride in mice, Eur. J. Pharmacol. 762 (2015) 411–418. S.K. Nazari, V. Nikoui, S. Ostadhadi, Z.H. Chegini, S. Oryan, A. Bakhtiarian, Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test, Pharmacol. Rep. (2016) (in press), Accepted Manuscript. A. Can, R.A. Blackwell, S.C. Piantadosi, D.T. Dao, K.C. O’Donnell, T.D. Gould, Antidepressant-like responses to lithium in genetically diverse mouse strains, Genes Brain Behav. 10 (4) (2011) 434–443. M. Newman, Lithium and the phosphoinositide hydrolysis second messenger system: a critical review of its therapeutic relevance, Lithium 2 (1991) 187– 194. R.H. Lenox, C.-G. Hahn, Overview of the mechanism of action of lithium in the brain: fifty-year update, J. Clin. Psychiatry 61 (2000) 5–15. J.P. Redrobe, M. Bourin, The effect of lithium administration in animal models of depression: a short review, Fundam. Clin. Pharmacol. 13 (3) (1999) 293–299. M. Ghasemi, H. Sadeghipour, A. Mosleh, H.R. Sadeghipour, A.R. Mani, A.R. Dehpour, Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test, Eur. Neuropsychopharmacol. 18 (5) (2008) 323–332. A. Sherman, F. Petty, Neurochemical basis of the action of antidepressants on learned helplessness, Behav. Neural Biol. 30 (2) (1980) 119–134. T. Hata, E. Itoh, H. Nishikawa, Behavioral characteristics of SART-stressed mice in the forced swim test and drug action, Pharmacol. Biochem. Behav. 51 (4) (1995) 849–853. F. Chenu, M. Bourin, Potentiation of antidepressant-like activity with lithium: mechanism involved, Curr. Drug Targets 7 (2) (2006) 159–163. T.D. Gould, K.C. O’Donnell, E.R. Dow, J. Du, G. Chen, H.K. Manji, Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test, Neuropharmacology 54 (3) (2008) 577– 587. I.N. Johnston, R.F. Westbrook, Inhibition of morphine analgesia by lithium: role of peripheral and central opioid receptors, Behav. Brain Res. 151 (1–2) (2004) 151–158. H. Homayoun, S. Khavandgar, A.R. Dehpour, The involvement of endogenous opioids and nitricoxidergic pathway in the anticonvulsant effects of footshock stress in mice, Epilepsy Res. 49 (2) (2002) 131–142. M. Konstandi, E. Johnson, M.A. Lang, M. Malamas, M. Marselos, Noradrenaline, dopamine, serotonin: different effects of psychological stress on brain biogenic amines in mice and rats, Pharmacol. Res. 41 (3) (2000) 341–346. D.C. McIntyre, P. Kent, S. Hayley, Z. Merali, H. Anisman, Influence of psychogenic and neurogenic stressors on neuroendocrine and central monoamine activity in fast and slow kindling rats, Brain Res. 840 (1) (1999) 65–74. K.D. Hale, D.A. Weigent, D.K. Gauthier, R.N. Hiramoto, V.K. Ghanta, Cytokine and hormone profiles in mice subjected to handling combined with rectal temperature measurement stress and handling only stress, Life Sci. 72 (13) (2003) 1495–1508. P. Marinelli, R. Quirion, C. Gianoulakis, An in vivo profile of b-endorphin release in the arcuate nucleus and nucleus accumbens following exposure to stress or alcohol, Neuroscience 127 (3) (2004) 777–784. T. Nabeshima, A. Katoh, T. Kameyama, Inhibition of enkephalin degradation attenuated stress-induced motor suppression (conditioned suppression of motility), J. Pharmacol. Exp. Ther. 244 (1) (1988) 303–309. P. Tejedor-Real, J.A. Mico, C. Smadja, R. Maldonado, B.P. Roques, J. GibertRahola, Involvement of d-opioid receptors in the effects induced by endogenous enkephalins on learned helplessness model, Eur. J. Pharmacol. 354 (1) (1998) 1–7. B.B. Land, M.R. Bruchas, J.C. Lemos, M. Xu, E.J. Melief, C. Chavkin, The dysphoric component of stress is encoded by activation of the dynorphin k-opioid system, J. Neurosci. 28 (2) (2008) 407–414. A. Saitoh, A. Sugiyama, T. Nemoto, H. Fujii, K. Wada, J.-I. Oka, H. Nagase, M. Yamada, The novel d opioid receptor agonist KNT-127 produces antidepressant-like and antinociceptive effects in mice without producing convulsions, Behav. Brain Res. 223 (2) (2011) 271–279. W.A. Carlezon, C. Béguin, J.A. DiNieri, M.H. Baumann, M.R. Richards, M.S. Todtenkopf, R.B. Rothman, Z. Ma, D.Y.-W. Lee, B.M. Cohen, Depressive-like effects of the é-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats, J. Pharmacol. Exp. Ther. 316 (1) (2006) 440–447. M. Ukai, M. Suzuki, T. Mamiya, Effects of U-50,488H, a k-opioid receptor agonist, on the learned helplessness model of depression in mice, J. Neural Transm. 109 (9) (2002) 1221–1225. E. Berrocoso, M.A.O. Rojas-Corrales, J.A. Micó, Non-selective opioid receptor antagonism of the antidepressant-like effect of venlafaxine in the forced swimming test in mice, Neurosci. Lett. 363 (1) (2004) 25–28. J.-L. Devoize, F. Rigal, A. Eschalier, J.-F. Trolese, M. Renoux, Influence of naloxone on antidepressant drug effects in the forced swimming test in mice, Psychopharmacology 84 (1) (1984) 71–75. S. Ide, S. Fujiwara, M. Fujiwara, I. Sora, K. Ikeda, M. Minami, G.R. Uhl, K. Ishihara, Antidepressant-like effect of venlafaxine is abolished in m-opioid receptor knockout mice, J. Pharmacol. Sci. 114 (1) (2010) 107. M.D.C. de Felipe, I. Jiménez, A. Castro, J. Fuentes, Antidepressant action of imipramine and iprindole in mice is enhanced by inhibitors of enkephalindegrading peptidases, Eur. J. Pharmacol. 159 (2) (1989) 175–180. M.P. Kaster, J. Budni, A.R. Santos, A.L.S. Rodrigues, Pharmacological evidence for the involvement of the opioid system in the antidepressant-like effect of
P. Khaloo et al. / Biomedicine & Pharmacotherapy 83 (2016) 1006–1015
[65]
[66]
[67]
[68]
[69]
[70]
[71]
[72]
[73]
[74]
[75]
[76] [77]
adenosine in the mouse forced swimming test, Eur. J. Pharmacol. 576 (1) (2007) 91–98. P.S. Brocardo, J. Budni, K.R. Lobato, A.R.S. Santos, A.L.S. Rodrigues, Evidence for the involvement of the opioid system in the antidepressant-like effect of folic acid in the mouse forced swimming test, Behav. Brain Res. 200 (1) (2009) 122– 127. A.D. Zomkowski, A.R. Santos, A.L. Rodrigues, Evidence for the involvement of the opioid system in the agmatine antidepressant-like effect in the forced swimming test, Neurosci. Lett. 381 (3) (2005) 279–283. P.S. Naidu, A.H. Lichtman, C.C. Archer, E.L. May, L.S. Harris, M.D. Aceto, NIH 11082 produces anti-depressant-like activity in the mouse tail-suspension test through a delta-opioid receptor mechanism of action, Eur. J. Pharmacol. 566 (1) (2007) 132–136. D.C. Broom, E.M. Jutkiewicz, J.E. Folk, J.R. Traynor, K.C. Rice, J.H. Woods, Nonpeptidic d-opioid receptor agonists reduce immobility in the forced swim assay in rats, Neuropsychopharmacology 26 (6) (2002) 744–755. M.M. Torregrossa, E.M. Jutkiewicz, H.I. Mosberg, G. Balboni, S.J. Watson, J.H. Woods, Peptidic delta opioid receptor agonists produce antidepressant-like effects in the forced swim test and regulate BDNF mRNA expression in rats, Brain Res. 1069 (1) (2006) 172–181. E. Berrocoso, K. Ikeda, I. Sora, G.R. Uhl, P. Sánchez-Blázquez, J.A. Mico, Active behaviours produced by antidepressants and opioids in the mouse tail suspension test, Int. J. Neuropsychopharmacol. 16 (1) (2013) 151–162. M. Rojas-Corrales, E. Berrocoso, J. Gibert-Rahola, J. Mico, Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats, Life Sci. 72 (2) (2002) 143–152. S.D. Mague, A.M. Pliakas, M.S. Todtenkopf, H.C. Tomasiewicz, Y. Zhang, W.C. Stevens, R.M. Jones, P.S. Portoghese, W.A. Carlezon, Antidepressant-like effects of k-opioid receptor antagonists in the forced swim test in rats, J. Pharmacol. Exp. Ther. 305 (1) (2003) 323–330. J.P. McLaughlin, M. Marton-Popovici, C. Chavkin, k Opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses, J. Neurosci. 23 (13) (2003) 5674–5683. J.P. McLaughlin, S. Li, J. Valdez, T.A. Chavkin, C. Chavkin, Social defeat stressinduced behavioral responses are mediated by the endogenous kappa opioid system, Neuropsychopharmacology 31 (6) (2006) 1241–1248. M.R. Bruchas, B.B. Land, M. Aita, M. Xu, S.K. Barot, S. Li, C. Chavkin, Stressinduced p38 mitogen-activated protein kinase activation mediates k-opioiddependent dysphoria, J. Neurosci. 27 (43) (2007) 11614–11623. A.T. Knoll, W.A. Carlezon Jr., Dynorphin, stress, and depression, Brain Res. 1314 (2010) 56–73. S.S. Newton, J. Thome, T.L. Wallace, Y. Shirayama, L. Schlesinger, N. Sakai, J. Chen, R. Neve, E.J. Nestler, R.S. Duman, Inhibition of cAMP response elementbinding protein or dynorphin in the nucleus accumbens produces an antidepressant-like effect, J. Neurosci. 22 (24) (2002) 10883–10890.
1015
[78] P.M. Beardsley, J.L. Howard, K.L. Shelton, F.I. Carroll, Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaineseeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats, Psychopharmacology 183 (1) (2005) 118– 126. [79] J.P. McLaughlin, B.B. Land, S. Li, J.E. Pintar, C. Chavkin, Prior activation of kappa opioid receptors by U50 488 mimics repeated forced swim stress to potentiate cocaine place preference conditioning, Neuropsychopharmacology 31 (4) (2006) 787–794. [80] M. Anjaneyulu, K. Chopra, Possible involvement of cholinergic and opioid receptor mechanisms in fluoxetine mediated antinociception response in streptozotocin-induced diabetic mice, Eur. J. Pharmacol. 538 (1) (2006) 80–84. [81] J. De Gandarias, E. Echevarria, I. Acebes, M. Silio, L. Casis, Effects of imipramine administration on mu-opioid receptor immunostaining in the rat forebrain, Arzneimittel-Forschung 48 (7) (1998) 717–719. [82] A. Dehpour, H. Farsam, M. Azizabadi-Farahani, Inhibition of the morphine withdrawal syndrome and the development of physical dependence by lithium in mice, Neuropharmacology 34 (1) (1995) 115–121. [83] A. Alborzi, S.E. Mehr, F. Rezania, S. Badakhshan, T. Mombeini, H. Shafaroodi, L. Moezi, M.N. Ravan, M. Sharifian, A.R. Dehpour, The effect of lithium chloride on morphine-induced tolerance and dependence in isolated guinea pig ileum, Eur. J. Pharmacol. 545 (2) (2006) 123–128. [84] H. Honar, K. Riazi, H. Homayoun, S. Demehri, M. Dehghani, K. Vafaie, M.R. Ebrahimkhani, N. Rashidi, S.A. Gaskari, A.R. Dehpour, Lithium inhibits the modulatory effects of morphine on susceptibility to pentylenetetrazoleinduced clonic seizure in mice: involvement of a nitric oxide pathway, Brain Res. 1029 (1) (2004) 48–55. [85] A. Dehpour, H. Farsam, M. Azizabadi-Farahani, The effect of lithium on morphine-induced analgesia in mice, Gen. Pharmacol. 25 (8) (1994) 1635– 1641. [86] P. Männistö, L. Saarnivaara, Effect of lithium on the analgesia caused by morphine and two antidepressants in mice, Pharmacology 8 (4–6) (1972) 329– 335. [87] R.B. Raffa, R.P. Martinez, Morphine antinociception is mediated through a LiCl-sensitive, IP3-restorable pathway, Eur. J. Pharmacol. 215 (2–3) (1992) 357–358. [88] R. Raffa, R. Martinez, M. Renzi, E. Codd, LiCl uncouples signal transduction in morphine-induced supraspinal antinociception in mice, Gen. Pharmacol. 26 (2) (1995) 317–320. [89] F. Tulunay, B. Kiran, S. Kaymakcalan, Interaction between morphine and lithium, Acta Med. Turc. 8 (1971) 51–60. [90] S. Amir, Involvement of endogenous opioids with forced swimming-induced immobility in mice, Physiol. Behav. 28 (2) (1982) 249–251. [91] S.P. Sivam, D.R. Smith, K. Takeuchi, J.-S. Hong, Lithium and haloperidol differentially alter the dynorphin A (1–8) and enkephalin levels in the neurointermediate lobe of rat pituitary, Neuropeptides 10 (3) (1987) 291–298.
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Original article
Lithium attenuated the behavioral despair induced by acute neurogenic stress through blockade of opioid receptors in mice Pegah Khalooa,b,1, Banafshe Sadeghia,b,1, Sattar Ostadhadia,c , Abbas Norouzi-Javidanc , Arya Haj-Mirzaiana,b , Samira Zolfagharied , Ahmad-Reza Dehpoura,b,* a
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran d Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran b c
A R T I C L E I N F O
Article history: Received 25 June 2016 Received in revised form 4 August 2016 Accepted 7 August 2016 Keywords: Lithium Opioid Neurogenic stress Forced swimming test Mice
A B S T R A C T
Major depressive disorder is disease with high rate of morbidity and mortality. Stressful events lead to depression and they can be used as a model of depression in rodents. In this study we aimed to investigate whether lithium modifies the stressed-induced depression through blockade of opioid receptors in mice. We used foot shock stress as stressor and forced swimming test (FST), tail suspension test (TST) and open field test (OFT) to evaluation the behavioral responses in mice. We also used naltrexone hydrochloride (as opioid receptor antagonist), and morphine (as opioid receptor agonist). Our results displayed that footshock stress significantly increased the immobility time in TST and FST but it could not change the locomotor behavior in OFT. When we combined the low concentrations of lithium and naltrexone a significant reduction in immobility time was seen in the FST and TST in comparison with control footshock stressed group administered saline only. Despite the fact that our data showed low concentrations of lithium, when administered independently did not significantly affect the immobility time. Also our data indicated that concurrent administration of lithium and naltrexone had no effect on open field test. Further we demonstrated that simultaneous administration of morphine and lithium reverses the antidepressant like effect of active doses of lithium. Our data acclaimed that we lithium can augment stressed-induced depression and opioid pathways are involved in this action. ã 2016 Published by Elsevier Masson SAS.
1. Introduction Major depressive disorder (MDD) is a disease with a high rate of mortality and morbidity [1]. Patients with MDD also suffer from other medical disorders including coronary artery disease, diabetes and cancer due to their depression [2]. Exposure to acute or chronic stress can lead to major depressive disorders [3]. It has been said that there is a relation between occurrence of depression and emotional stress in individuals [4], Therefore acute or chronic stress induction in rodents are widely used as a model of depression [5] Several studies support the antidepressant effect of lithium especially in treatment resistant depression [6,7] Even some studies suggest that lithium may augment the anti-suicidal effects
* Corresponding author at: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran. E-mail address: [email protected] (A.-R. Dehpour). 1 Both authors have contributed equally to this project. http://dx.doi.org/10.1016/j.biopha.2016.08.015 0753-3322/ã 2016 Published by Elsevier Masson SAS.
of other antidepressant drugs and it can reduce the risk of complete suicide in adult patients with unipolar depression [6]. Though the effects of lithium on patients with bipolar mood disorder are more clear [8]. Moreover it has been said that lithium alters stress-induced changes in mouse hippocampus [9]. Lithium treatment may also modifies long term effect of stress on neuropeptide Y, This protein is suggested to play a role in development of depression [10]. However the definite mechanism for antidepressant effect of lithium is still unknown. There are many hypotheses. There are some evidence that indicate an association between opioid analgesic exposure and symptoms of depression [11]. An association between duration of opioid analgesic use and the risk of development of depression has also been discussed [11]. The change in mu-opioid receptors also results in normalizing stress-induced depression in rodents [5]. For"show_abs example it has been suggested that opioid receptors alone or in combination with N-methyl-D-aspartate have a role in protective effect of fluoxetine against the depressive-like behavior induced by acute stress [12].
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In addition studies suggest that lithium is effective on opioid receptors in rat brain [13]. For example mu-opioid receptor expression reveals an increase by chronic lithium treatment [14]. It has been shown that the motivational effect of lithium is a result of its influence on opioid receptors in the central nervous system [15]. The aim of this study is to investigate whether opioid systems are involved in the protective effect of lithium treatment against behavioral despair induced by acute stress. To examine this hypothesis we used foot shock stress as a stressor and also forced swimming test, tail suspension test and open field test to evaluate animal behavioral responses to stress.
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2.5. Open-field test (OFT) Locomotion behavior of animals in response to drugs was evaluated by an Open-field test [23]. Immediately after 30 min foot-shock stress, mice were gently removed from the box and were separately placed in open field apparatus. The open-field apparatus consisted of a wooden box (60 cm 50 cm 40 cm) which was divided into 12 squares. Each mouse was placed gently in the center of the field and behavior was recorded by counting the number of squares crossing for 6 min. After each test, the surface of the apparatus was cleaned with solution of 70% ethanol to hide animal clues. Each mouse was used in only one experiment [24].
2. Material and methods 2.6. Tail suspension test (TST) 2.1. Animals Male adult NMRI (Naval Medical Research Institute) mice (Pasture institute of Iran) weighting 21–30 g were used throughout the study. The animals were housed in groups of six to seven in Plexiglas boxes (25 25 15) under standard conditions (12-h light-dark cycle, temperature 24 2 C). Animals had free access to food and water aside from the period they were removed from cages to be tested. All behavioral experiments were performed between 8:00 a.m. and 14:00 p.m. Also, each experimental group contained 6–8 animals. All procedures in this study were carried out in accordance with institutional guidelines for animal care and use (Department of Pharmacology, School of Medicine, TUMS). 2.2. Drugs and treatment The following drugs were used in this study: Naltrexone hydrochloride, Lithium chloride and Morphine Sulfate. All drugs were dissolved in physiological saline .All drugs in different doses were prepared in constant volume of 1 mg/kg immediately before the experiments. All injections were administered intraperitoneally (i.p.) but Morphine Sulfate was administered subcutaneous (S.C). 2.3. Foot-shock stress Stress was induced by a picket box (30 30 40 cm3 high) with a steel-rod floor (29 parallel rods, 0.3 cm in diameter set one cm apart). Inevitable foot-shock (3-mA scrambled shock stimulus, 50Hz) was delivered through a scrambler to the grid ground [16,17]. Animals were exposed to intermittent foot-shock for thirty minutes (Five-s pulses delivered each 30 s for 30 min). Animals were allowed to adopt with the equipment for thirty minutes just before stress induction [12,18]. Right away after this point mice were placed in the open field equipment. On the day of the experiments, right away after FSS, each mouse was mildly removed from this box and evaluated by one of the behavioral tests. It was not possible to perform more than one behavioral test in each animal, since the behavioral tasks are supposed to be conducted immediately after stress exposure. 2.4. Forced swimming test (FST) Immediately after 30 min foot-shock stress, mice were gently removed from the box and were separately placed in an open glass cylinder (diameter: 10 cm, height: 25 cm) filled with 19 cm of water at 23 1 C and allowed to swim for 6 min [19–21]. The method of Porsolt et al. was used for evaluating depression in rodents [22]. Immobility behavior was considered when the animal was without motion except keeping the head above the water for survive. The immobility time was recorded during the last 4 min of the test by two expert raters.
The tail suspension test was conducted as previously described by Steru et al. [25]. Immediately after 30 min foot-shock stress, mice were gently removed from the box and were separately evaluated in TST. Animals were individually suspended by the tail 50 cm above the table top by using an adhesive tape placed 1 cm from the tip. Test lasted for 6 min and mice were considered to be immobile when they were motionless or hung passively by 2 blind observers to result [26,27]. 2.7. Experimental procedure Initially, we determined the effect of acute FSS on the mice immobility time in the FST and TST and also the locomotor activity in the OFT. In the next experiment we acquired the effective and subeffective doses of lithium in behavioral tests. For this purpose, animals (with/without experience to FSS) were injected by lithium (1 and 5 and 10 mg/kg) [8,28,29].immediately before exposure to intermittent foot-shock stress and 30 min [8,28,29].before beginning of behavioral tests (locomotor behavior in OFT and the time of immobility in FST or TST). Saline (5 mL/kg) was administrated into control animals to exclude the effect of saline injection on the animals’ behavior. Next, we tried to examine the probable involvement of opioid system in this effects of lithium. So, subeffective dose of naltrexone (0.3 mg/kg) [12,18,30] was coinjected with the subeffective dose of lithium in stressed/nonstressed mice on FST, TST, or OFT. Also, subeffective doses of opioid receptor agonists morphine (1 mg/kg) was applied in our subsequent test, with the effective dose of lithium. Morphine Sulfate was injected immediately before exposure to intermittent foot-shock stress and 30 min before behavioral tests beginning [12,30]. 2.8. Statistical analysis Statistical analyses were carried out using GraphPad Prism 5 software (San Diego, CA, USA). The results are presented as mean + S.E.M. One-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test was carried out to evaluation of dose-related effects of lithium on immobility time, locomotor activity. Two-way ANOVA followed by Bonferroni test was used to analyze the other results. The analysis method applied in each part of the experiment is stated in the Section 3 and “Fig. captions”. Data are expressed as mean + S.E.M. P values less than 0.05 were considered statistically significant. 3. Results 3.1. Effect of acute FSS on the animals behavior in the behavioral tests Fig. 1 shows changes in motor activity and immobility time in mice response to foot-shock exposure in the acute foot-shock stress in acute stress experiment. Depressive effect of foot-shock
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Fig. 1. Effect of acute foot-shock stress (FSS) on behavioral tests. Effect of acute FSS on duration of immobility in forced swimming test (FST) (A) and tail suspension test (TST) (B), and number of crossing in open field test (OFT) (C). Acute-FSS animals were exposed to prolonged, intermittent foot-shock for 30 min and then were immediately evaluated in behavioral tests (D). Values are expressed as the mean SEM; **p < 0.01 vs. control group.
stress was determined in the FST (Fig. 1A) and TST (Fig. 1B). In the OFT (Fig. 1C) no significant changes were observed (p > 0.05). 3.1. Effect of lithium on depressive-like behaviors induced by acute FSS Antidepressant-like effects of Lithium (1, 5, 10 mg/kg i.p.) administered 30 min before FST and TST are shown in Fig. 2. In nonstressed condition, these doses did not have effects on nonstressed mice compared to saline-administered mice in both FST (Fig. 2A) and TST (Fig. 2C). In other hand lithium reversed immobility time induced by foot-shock stress at dose of 5 mg/kg (p 0 < 0.01) and 10 mg/kg (p 0 < 0.001) despite 1 mg/kg did not show antidepressant-like effect in the FST (Fig. 2B). Also acute administration of lithium at dose of 10 mg/kg (p 0 < 0.01) reversed the behavioral despair induced by acute electric shock stress in the TST (Fig. 2D). Fig. 3 shows either in stressed and non-stressed mice, lithium at the administered doses mentioned above did not remarkably changed locomotor activity in the open-field test(p > 0.05). 3.2. Effect of opioid receptors in the antidepressant-like effect of lithium in stressed animals Fig. 4 shows that naltrexone (0.3 mg/kg) did not reduce immobility time in non-stressed mice in both FST (Fig. 4A) and TST (Fig. 4C), neither did in acutely stressed animals in FST (Fig. 4B) and TST (Fig. 4D). In stressed condition, the co-administration of sub-effective doses of lithium (1 mg/kg) and Naltrexone (0.3 mg/ kg) significantly reduced the immobility time in FST (p < 0.001) and TST (p < 0.01) in comparison with control foot-shock stressed group (Fig. 4B and D) while concurrent administration of
naltrexone and lithium did not have effect on open-field test (Fig. 5A and B). Fig. 6 shows that morphine (1 mg/kg) injection did not affect the immobility time in non-stressed and stressed situations (p > 0.05, Fig. 6A–D), but co-administration of an effective dose of lithium (10 mg/kg) with morphine (1 mg/kg) significantly reversed the anti-immobility effect of lithium in acute-FSS group in both FST (p < 0.01, Fig. 6B) and TST (p < 0.01, Fig. 6D), while this treatment did not alter the immobility of non-stressed animals in FST and TST (p > 0.05, Fig. 6A and C). These treatments did not display any significant alterations in the locomotor behaviors (p > 0.05, Fig. 7A and B) of both non-stressed and stressed animals in the OFT. 4. Discussion In current report, we have revealed that induction of acute stress display depressant effect and significantly amplifies the immobility time period in the mice FST and TST. [31]. Previous investigations displayed that uncontrollable shock produces a behavioral deficit and numerous acute stress procedures are accepted as animal paradigms of depressive, though in these models, the time range for determining the behavioral alterations relative to stress is short compared with the long-lasting property of the human disorders[31]. In accordance with previous reports, we presented that acute FSS produced depressive-like behaviors in mice [12,18,30,32]. Also it was showed that the rats immobility period in FST was augmented by acute but not chronic restraint stress, which was then inhibited by naloxone as opioid receptor antagonist [33]. Anisman et al. have presented that acute FSS as an acute neurogenic stressor could stimulate distinct molecular
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Fig. 2. Effect of lithium on behavioral tests. Effect of acute administration of lithium on duration of immobility of non-stressed (NS) and stressed (FSS) mice in forced swimming test (FST) (A, B) and tail suspension test (TST) (C, D) .Lithium at doses of 1, 5 and 10 mg/kg adminestrated 30 min before FST or TST (E). Values are expressed as the mean SEM; ***p < 0.00,1 **p < 0.01 vs. saline-treated group. FSS, foot-shock stress.
Fig. 3. Effect of lithium on behavioral tests. Effect of acute administration of lithium on number of crossing of non-stressed (NS) (A) and stressed (FSS) (B) mice in open field test (OFT). Lithium at doses of 1, 5 and 10 mg/kg administrated 30 min before OFT (E).FSS, foot-shock stress.
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Fig. 4. Effect of treatment with naltrexone (NTX) and its combination with lithium. Effect of administration of NTX (0.3 mg/kg) and its combination with lithium (1 mg/kg) on duration of immobility of non-stressed (NS) and stressed (FSS) mice in forced swimming test (FST) (A, B) and tail suspension test (TST) (C, D). Lithium and/or NTX administrated 30 min before FST or TST(E). Values are expressed as the mean SEM; ***p < 0.001 and **p < 0.01 vs. saline-treated group. FSS, foot-shock stress.
pathways and behavioral effects which are connected to the depression in rodents [34]. In current report behavioral tests including FST and TST, which are well known screening methods for agents with antidepressant effectiveness, were applied in the investigations. Numerous animal paradigms for depression are being applied, FST and TST are the most widely used screening test for antidepressant property in rodents [22,25,35]. The immobile performance reveals behavioral despair which is a disappointment to persevere in escape-directed behavior after stress [35,36]. Meaningful decrease in the time of immobility in these paradigms
after treatment is reflected as a probable antidepressant-like effectiveness of the treatment. Although the FST and TST are quite tried and trusted, false negative consequences might be acquired in sedation and sickness circumstances and also false positive outcomes are sometimes detected with agents which have stimulant effects. Consequently, the locomotor activity is normally assessed in each investigational group to exclude the potential effects of situations and treatments on animals’ locomotor behavior [35,37,38]. The results we obtained from this report appears not to be related with motoric alterations, since animals in
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Fig. 5. Effect of administration of NTX (0.3 mg/kg) and its combination with lithium (1 mg/kg) on number of crossing of non-stressed (NS) (A) and stressed (FSS) (B) mice in open field test (OFT). Lithium and/or NTX administrated 30 min before FST or TST (E). FSS, foot-shock stress.
different groups did not display any significant variations in ambulation in the OFT. Also in present study we evaluated the effect of lithium on depression that induced by acute FSS. Our results showed that the stress-induced immobility in mice is inhibited by acute injection of lithium, in doses tend to be subeffective in none-stressed mice. Lithium is one of these drugs that decrease the immobility time of mice in FST and TST [8]. but the response varies in different strains of mouse [39]. Lithium is the drug of choice for the of mania treatment and bipolar affective disorders prophylaxis, but its molecular mechanisms of action stay poorly recognized [40,41]. Numerous reports also have stated that acute lithium administration decreases immobility time in mice [42,43]. Interestingly, lithium administration also equivalents the property of antidepressants on learned helplessness [44] and immobilization stress in rats [45]. However the definite mechanism for antidepressant effect of lithium is still unknown, there are many hypotheses. One that has been suggested is an enhancement of serotonergic transmission [46]. NMDA receptors signaling [28] and nitric oxide involvement are other hypothesis about lithium mechanisms [8]. Some studies have also demonstrated the role of a-amino-3-hydroxy-5-methyl4isoxazolepropionic acid (AMPA) receptors [47]. Moreover studies have suggested an interaction between lithium and opioid receptors [48]. It has been said the influence of lithium on the treatment of affective illness shares certain actions on opioid receptors in the brain [13]. So in the next step we have assessed the possible involvement of opioid system in lithium inhibitory effect on depressant-like behavior induced by FSS, since opioid tone increases during stress
[49]. In this regards, subeffective doses of opioid receptor antagonist was coadministered with the subeffective dose of lithium in stressed/non-stressed animals. In the present study when we combined the low concentrations of lithium and naltrexone, a significant reduction in immobility time was seen in the FST and TST in comparison with control group. Further we demonstrated that simultaneous administration of morphine and lithium reverses the antidepressant like effect of effective doses of lithium in stressed-mice. Stressful conditions change CNS functions by altering numerous neurotransmitters, endocrine and neuroendocrine systems, mainly monoamines, steroids and neurosteroids [50,51]. The expression and release [52,53] of endogenous opioids in brain enhances subsequent stress experience unconnected to the nature of the stressor. Endogenous opioids display their effects by acting on delta (DOR), kappa (KOR) and mu (MOR) receptors, each with their distinct cellular reactions. Some preceding reports have specified that opioid agonists induce an antidepressant-like effect [54,55]. It was displayed that activation of DOR receptor by met-enkephalin produce antidepressant-like effect in rodents [56,57], however, dynorphin, which stimulates KOR, probably induces depressive like effects [58,59]. Previous studies have revealed that the stimulation of the opioid pathway is involved in the mechanisms underlying the effect of antidepressants [60–63]. Furthermore, the opioid system is also participated in the mechanisms of action of agents such as adenosine [64], folic acid [65] and agmatine [66] that induced an antidepressant-like effects in the FST. These informations showed that the antidepressant effect of these agents was mainly mediated by MOR and DOR stimulation and an inhibition of KOR.
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It has been revealed that opioid receptors differentially and diFig. 6. Effect of treatment with morphine (MOR) and its combination with lithium. Effect of administration of MOR (1 mg/kg) and its combination with lithium (10 mg/kg) on s- duration of immobility of non-stressed (NS) and stressed (FSS) mice in forced swimming test (FST) (A, B) and tail suspension test (TST) (C, D). Lithium and/or MOR t- administrated 30 min before FST or TST (E). Values are expressed as the mean SEM; ***p < 0.001 and **p < 0.01 vs. saline-treated group. #p < 0.05 and ##p < 0.01 vs. lithium i- treated group. FSS, foot-shock stress. nctly involve in the behavioral reactions. Numerous reports have antagonists or by ablation of the genes encoding KORs [72,73, displayed that administration of DOR agonists produced an 75–79]. antidepressant-like effects in FST [67–69]. Equally, injection of The results of our previous report [30], display that inhibition of MOR agonists has been stated to decrease the depressive-like opioid receptors by non-selective antagonist, naltrexone which behaviors in some reports [70,71]. In contrast, KOR agonists blocks all the subtypes of opioid receptors, inhibited the administration has been exposed to induce depressive-like effects immobility time enhancement produced by foot shock stress. in the FST [58]. Also, KOR antagonists have an antidepressant-like There were numerous evidence demonstrating the effects of property in rodents after administration [72,73]. antidepressant on opioid system [63,80,81] and the involvement of Stress stimulates the release of dynorphin, which activates opioids in the pathophysiology of depression. But there were no KORs in the central nervous systems [73–75]. Evidence indicated reports to demonstrate the participation of opioid system in that the acute outcomes of stress are triggered, at least in part, by mediating the antidepressant-like effect of lithium in an animal dynorphin-related KOR stimulation [76]. It was showed that the model of depression. prodepressive-like effects of stress in rodents are reduced by KOR
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Fig. 7. Effect of administration of MOR (1 mg/kg) and its combination with lithium (1 mg/kg) on number of crossing of non-stressed (NS) (A) and stressed (FSS) (B) mice in open field test (OFT). Lithium and/or MOR administrated 30 min before OFT (C). FSS, foot-shock stress.
Numerous reports have also revealed the communication between the lithium and the opioid system. For instance, lithium can decrease morphine tolerance and dependence [82,83], and prevent modulatory properties of morphine on pentylenetetrazole-induced seizure in mice [84]. Furthermore, acute and chronic injection of lithium to rodents may increase or decrease opioidinduced analgesia [85–89], and enhance sensitivity to naloxone as opioid receptor antagonist [90]. In fact, the stated interruption of opioid receptor activity by lithium may suggest possible profits in definite clinical conditions. It has been displayed that lithium produces a reduction in the level of dynorphin (endogenous ligand for KOR) concentration in rat brain [91] . So this is hypothesis that lithium antidepressant effect in stressed-mice is mediated, at least in part, by inhibition of release of dynorphin and finally inhibition of KOR pathway. But there are no studies on the interaction of antidepressant effect of lithium with these subtypes of opioid receptors on FST or TST, neither about the interaction of specific agonists and antagonists of these subtypes with the antidepressant action of lithium in FSS. The present report does not include data on what opioid receptor subtypes including mu, kappa, and delta, participate the antidepressant effect of lithium, so additional experiments are necessary. In conclusion, our results acclaimed that antidepressant-like effect of lithium is opioid mediated. For the first time we showed that lithium attenuate the stress- induced depression in mice and this action is mediated through the opioid pathway. Even so, further studies are necessary to discover the benefits of clinically applied opioid antagonists beside standard antidepressants. References [1] M. Salehi-Sadaghiani, M. Javadi-Paydar, M.H. Gharedaghi, A. Zandieh, P. Heydarpour, Y. Yousefzadeh-Fard, A.R. Dehpour, NMDA receptor involvement in antidepressant-like effect of pioglitazone in the forced swimming test in mice, Psychopharmacology (Berl.) 223 (3) (2012) 345–355.
[2] A.S. Heller, Cortical-subcortical interactions in depression: from animal models to human psychopathology, Front. Syst. Neurosci. 10 (2016) 20. [3] F. Chaouloff, A. Hemar, O. Manzoni, Acute stress facilitates hippocampal CA1 metabotropic glutamate receptor-dependent long-term depression, J. Neurosci. 27 (27) (2007) 7130–7135. [4] Y.K. Kim, N.H. Cha, Correlations among occupational stress, fatigue, and depression in call center employees in Seoul, J. Phys. Ther. Sci. 27 (10) (2015) 3191–3194. [5] F.R. Wang, M.Q. Qiao, L. Xue, S. Wei, Possible involvement of micro opioid receptor in the antidepressant-like effect of Shuyu formula in restraint stressinduced depression-like rats, Evid. Based Complement. Altern. Med. 2015 (2015) 452412. [6] A. Cipriani, F. Girlanda, E. Agrimi, A. Barichello, R. Beneduce, I. Bighelli, G. Bisoffi, A. Bisogno, P. Bortolaso, M. Boso, C. Calandra, L. Cascone, C. Corbascio, V.F. Parise, F. Gardellin, D. Gennaro, B. Hanife, C. Lintas, M. Lorusso, C. Luchetta, C. Lucii, F. Cernuto, F. Tozzi, A. Marsilio, F. Maio, C. Mattei, D. Moretti, M.G. Appino, M. Nose, G. Occhionero, D. Papanti, D. Pecile, M. Purgato, D. Prestia, F. Restaino, T. Sciarma, A. Ruberto, S. Strizzolo, S. Tamborini, O. Todarello, S. Ziero, S. Zotos, C. Barbui, Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial, BMC Psychiatry 13 (2013) 212. [7] T. Bschor, M. Adli, C. Baethge, U. Eichmann, M. Ising, M. Uhr, S. Modell, H. Kunzel, B. Muller-Oerlinghausen, M. Bauer, Lithium augmentation increases the ACTH and cortisol response in the combined DEX/CRH test in unipolar major depression, Neuropsychopharmacology 27 (3) (2002) 470–478. [8] M. Ghasemi, H. Sadeghipour, A. Mosleh, H.R. Sadeghipour, A.R. Mani, A.R. Dehpour, Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test, Eur. Neuropsychopharmacol. 18 (5) (2008) 323–332. [9] S. Yoshida, M. Maeda, S. Kaku, H. Ikeya, K. Yamada, S. Nakaike, Lithium inhibits stress-induced changes in tau phosphorylation in the mouse hippocampus, J. Neural Transm. (Vienna) 113 (11) (2006) 1803–1814. [10] H. Husum, A.A. Mathe, Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes, Neuropsychopharmacology 27 (5) (2002) 756–764. [11] J.F. Scherrer, D.M. Svrakic, K.E. Freedland, T. Chrusciel, S. Balasubramanian, K.K. Bucholz, E.V. Lawler, P.J. Lustman, Prescription opioid analgesics increase the risk of depression, J. Gen. Intern. Med. 29 (3) (2014) 491–499. [12] A. Haj-Mirzaian, N. Kordjazy, S. Ostadhadi, S. Amiri, A. Haj-Mirzaian, A. Dehpour, Fluoxetine reverses the behavioral despair induced by neurogenic stress in mice: role of N-methyl-d-aspartate and opioid receptors, Can. J. Physiol. Pharmacol. 94 (6) (2016) 599–612. [13] K. Stengaard-Pedersen, M. Schou, Opioid peptides and receptors in relation to affective illness. Effects of desipramine and lithium on opioid receptors in rat brain, Acta Pharmacol. Toxicol. (Copenh.) 56 (Suppl. 1) (1985) 170–179.
1014
P. Khaloo et al. / Biomedicine & Pharmacotherapy 83 (2016) 1006–1015
[14] M.R. Zarrindast, A. Lahmi, S. Ahamadi, Possible involvement of mu-opioid receptors in effect of lithium on inhibitory avoidance response in mice, J. Psychopharmacol. 22 (8) (2008) 865–871. [15] T.S. Shippenberg, M.J. Millan, R.F. Mucha, A. Herz, Involvement of betaendorphin and mu-opioid receptors in mediating the aversive effect of lithium in the rat, Eur. J. Pharmacol. 154 (2) (1988) 135–144. [16] J.W. Lewis, J.T. Cannon, J.C. Liebeskind, Opioid and nonopioid mechanisms of stress analgesia, Science 208 (4444) (1980) 623–625. [17] J.T. Madden, H. Akil, R.L. Patrick, J.D. Barchas, Stress-induced parallel changes in central opioid levels and pain responsiveness in the rat, Nature 265 (5592) (1977) 358–360. [18] S. Ostadhadi, A. Haj-Mirzaian, V. Nikoui, N. Kordjazy, A.R. Dehpour, Involvement of opioid system in antidepressant-like effect of the cannabinoid CB1 receptor inverse agonist AM-251 after physical stress in mice, Clin. Exp. Pharmacol. Physiol. 43 (2) (2016) 203–212. [19] S. Ostadhadi, M.I. Khan, A. Norouzi-Javidan, M. Chamanara, F. Jazaeri, S. Zolfaghari, A.-R. Dehpour, Involvement of NMDA receptors and l-arginine/ nitric oxide/cyclic guanosine monophosphate pathway in the antidepressantlike effects of topiramate in mice forced swimming test, Brain Res. Bull. 122 (2016) 62–70. [20] M.I. Khan, S. Ostadhadi, S. Zolfaghari, S.E. Mehr, G. Hassanzadeh, A.-R. Dehpour, The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test, Neurosci. Lett. 612 (2016) 52–61. [21] S. Ostadhadi, M.I. Khan, A. Norouzi-Javidan, A.-R. Dehpour, Antidepressant effect of pramipexole in mice forced swimming test: a cross talk between dopamine receptor and NMDA/nitric oxide/cGMP pathway, Biomed. Pharmacother. 81 (2016) 295–304. [22] R. Porsolt, A. Bertin, M. Jalfre, Behavioral despair in mice: a primary screening test for antidepressants, Arch. Int. Pharm. Thér. 229 (2) (1977) 327–336. [23] S. Ostadhadi, M. Ahangari, V. Nikoui, A. Norouzi-Javidan, S. Zolfaghari, F. Jazaeri, M. Chamanara, R. Akbarian, A.-R. Dehpour, Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test, Biomed. Pharmacother. 82 (2016) 713–721. [24] S. Ostadhadi, N. Kordjazy, A. Haj-Mirzaian, S. Ameli, G. Akhlaghipour, A. Dehpour, Involvement of NO/cGMP pathway in the antidepressant-like effect of gabapentin in mouse forced swimming test, Naunyn-Schmiedeberg’s Arch. Pharmacol. 389 (4) (2016) 393–402. [25] L. Steru, R. Chermat, B. Thierry, P. Simon, The tail suspension test: a new method for screening antidepressants in mice, Psychopharmacology (Berl.) 85 (3) (1985) 367–370. [26] N. Kordjazy, A. Haj-Mirzaian, S. Amiri, S. Ostadhadi, H. Amini-khoei, A.R. Dehpour, Involvement of N-methyl-D-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test, Pharmacol. Biochem. Behav. 141 (2016) 1–9. [27] A. Haj-Mirzaian, N. Kordjazy, S. Amiri, A. Haj-Mirzaian, H. Amini-khoei, S. Ostadhadi, A. Dehpour, Involvement of nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tropisetron and ondansetron in mice forced swimming test and tail suspension test, Eur. J. Pharmacol. 780 (2016) 71–81. [28] M. Ghasemi, M. Raza, A.R. Dehpour, NMDA receptor antagonists augment antidepressant-like effects of lithium in the mouse forced swimming test, J. Psychopharmacol. 24 (4) (2010) 585–594. [29] A. Bahremand, S.E. Nasrabady, P. Ziai, R. Rahimian, T. Hedayat, B. Payandemehr, A.R. Dehpour, Involvement of nitric oxide-cGMP pathway in the anticonvulsant effects of lithium chloride on PTZ-induced seizure in mice, Epilepsy Res. 89 (2–3) (2010) 295–302. [30] A. Haj-Mirzaian, S. Ostadhadi, N. Kordjazy, A.R. Dehpour, S. Ejtemaei Mehr, Opioid/NMDA receptors blockade reverses the depressant-like behavior of foot shock stress in the mouse forced swimming test, Eur. J. Pharmacol. 735 (2014) 26–31. [31] H.H. Van Dijken, J.A. Van Der Heyden, J. Mos, F.J. Tilders, Inescapable footshocks induce progressive and long-lasting behavioural changes in male rats, Physiol. Behav. 51 (4) (1992) 787–794. [32] J.M. Weiss, P.A. Goodman, B.G. Losito, S. Corrigan, J.M. Charry, W.H. Bailey, Behavioral depression produced by an uncontrollable stressor: relationship to norepinephrine, dopamine, and serotonin levels in various regions of rat brain, Brain Res. Rev. 3 (2) (1981) 167–205. [33] L. Cancela, S. Rossi, V. Molina, Effect of different restraint schedules on the immobility in the forced swim test: modulation by an opiate mechanism, Brain Res. Bull. 26 (5) (1991) 671–675. [34] H. Anisman, S. Hayley, O. Kelly, T. Borowski, Z. Merali, Psychogenic, neurogenic, and systemic stressor effects on plasma corticosterone and behavior: mouse strain-dependent outcomes, Behav. Neurosci. 115 (2) (2001) 443. [35] J.F. Cryan, A. Markou, I. Lucki, Assessing antidepressant activity in rodents: recent developments and future needs, Trends Pharmacol. Sci. 23 (5) (2002) 238–245. [36] A. Haj-Mirzaian, N. Kordjazy, A. Haj-Mirzaian, S. Ostadhadi, M. Ghasemi, S. Amiri, M. Faizi, A. Dehpour, Evidence for the involvement of NMDA receptors in the antidepressant-like effect of nicotine in mouse forced swimming and tail suspension tests, Psychopharmacology 232 (19) (2015) 3551–3561. [37] N. Kordjazy, A. Haj-Mirzaian, S. Amiri, S. Ostadhadi, M. Kordjazy, M. Sharifzadeh, A.R. Dehpour, Elevated level of nitric oxide mediates the anti-
[38]
[39]
[40]
[41] [42] [43]
[44] [45]
[46] [47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
[57]
[58]
[59]
[60]
[61]
[62]
[63]
[64]
depressant effect of rubidium chloride in mice, Eur. J. Pharmacol. 762 (2015) 411–418. S.K. Nazari, V. Nikoui, S. Ostadhadi, Z.H. Chegini, S. Oryan, A. Bakhtiarian, Possible involvement of ATP-sensitive potassium channels in the antidepressant-like effect of baclofen in mouse forced swimming test, Pharmacol. Rep. (2016) (in press), Accepted Manuscript. A. Can, R.A. Blackwell, S.C. Piantadosi, D.T. Dao, K.C. O’Donnell, T.D. Gould, Antidepressant-like responses to lithium in genetically diverse mouse strains, Genes Brain Behav. 10 (4) (2011) 434–443. M. Newman, Lithium and the phosphoinositide hydrolysis second messenger system: a critical review of its therapeutic relevance, Lithium 2 (1991) 187– 194. R.H. Lenox, C.-G. Hahn, Overview of the mechanism of action of lithium in the brain: fifty-year update, J. Clin. Psychiatry 61 (2000) 5–15. J.P. Redrobe, M. Bourin, The effect of lithium administration in animal models of depression: a short review, Fundam. Clin. Pharmacol. 13 (3) (1999) 293–299. M. Ghasemi, H. Sadeghipour, A. Mosleh, H.R. Sadeghipour, A.R. Mani, A.R. Dehpour, Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test, Eur. Neuropsychopharmacol. 18 (5) (2008) 323–332. A. Sherman, F. Petty, Neurochemical basis of the action of antidepressants on learned helplessness, Behav. Neural Biol. 30 (2) (1980) 119–134. T. Hata, E. Itoh, H. Nishikawa, Behavioral characteristics of SART-stressed mice in the forced swim test and drug action, Pharmacol. Biochem. Behav. 51 (4) (1995) 849–853. F. Chenu, M. Bourin, Potentiation of antidepressant-like activity with lithium: mechanism involved, Curr. Drug Targets 7 (2) (2006) 159–163. T.D. Gould, K.C. O’Donnell, E.R. Dow, J. Du, G. Chen, H.K. Manji, Involvement of AMPA receptors in the antidepressant-like effects of lithium in the mouse tail suspension test and forced swim test, Neuropharmacology 54 (3) (2008) 577– 587. I.N. Johnston, R.F. Westbrook, Inhibition of morphine analgesia by lithium: role of peripheral and central opioid receptors, Behav. Brain Res. 151 (1–2) (2004) 151–158. H. Homayoun, S. Khavandgar, A.R. Dehpour, The involvement of endogenous opioids and nitricoxidergic pathway in the anticonvulsant effects of footshock stress in mice, Epilepsy Res. 49 (2) (2002) 131–142. M. Konstandi, E. Johnson, M.A. Lang, M. Malamas, M. Marselos, Noradrenaline, dopamine, serotonin: different effects of psychological stress on brain biogenic amines in mice and rats, Pharmacol. Res. 41 (3) (2000) 341–346. D.C. McIntyre, P. Kent, S. Hayley, Z. Merali, H. Anisman, Influence of psychogenic and neurogenic stressors on neuroendocrine and central monoamine activity in fast and slow kindling rats, Brain Res. 840 (1) (1999) 65–74. K.D. Hale, D.A. Weigent, D.K. Gauthier, R.N. Hiramoto, V.K. Ghanta, Cytokine and hormone profiles in mice subjected to handling combined with rectal temperature measurement stress and handling only stress, Life Sci. 72 (13) (2003) 1495–1508. P. Marinelli, R. Quirion, C. Gianoulakis, An in vivo profile of b-endorphin release in the arcuate nucleus and nucleus accumbens following exposure to stress or alcohol, Neuroscience 127 (3) (2004) 777–784. T. Nabeshima, A. Katoh, T. Kameyama, Inhibition of enkephalin degradation attenuated stress-induced motor suppression (conditioned suppression of motility), J. Pharmacol. Exp. Ther. 244 (1) (1988) 303–309. P. Tejedor-Real, J.A. Mico, C. Smadja, R. Maldonado, B.P. Roques, J. GibertRahola, Involvement of d-opioid receptors in the effects induced by endogenous enkephalins on learned helplessness model, Eur. J. Pharmacol. 354 (1) (1998) 1–7. B.B. Land, M.R. Bruchas, J.C. Lemos, M. Xu, E.J. Melief, C. Chavkin, The dysphoric component of stress is encoded by activation of the dynorphin k-opioid system, J. Neurosci. 28 (2) (2008) 407–414. A. Saitoh, A. Sugiyama, T. Nemoto, H. Fujii, K. Wada, J.-I. Oka, H. Nagase, M. Yamada, The novel d opioid receptor agonist KNT-127 produces antidepressant-like and antinociceptive effects in mice without producing convulsions, Behav. Brain Res. 223 (2) (2011) 271–279. W.A. Carlezon, C. Béguin, J.A. DiNieri, M.H. Baumann, M.R. Richards, M.S. Todtenkopf, R.B. Rothman, Z. Ma, D.Y.-W. Lee, B.M. Cohen, Depressive-like effects of the é-opioid receptor agonist salvinorin A on behavior and neurochemistry in rats, J. Pharmacol. Exp. Ther. 316 (1) (2006) 440–447. M. Ukai, M. Suzuki, T. Mamiya, Effects of U-50,488H, a k-opioid receptor agonist, on the learned helplessness model of depression in mice, J. Neural Transm. 109 (9) (2002) 1221–1225. E. Berrocoso, M.A.O. Rojas-Corrales, J.A. Micó, Non-selective opioid receptor antagonism of the antidepressant-like effect of venlafaxine in the forced swimming test in mice, Neurosci. Lett. 363 (1) (2004) 25–28. J.-L. Devoize, F. Rigal, A. Eschalier, J.-F. Trolese, M. Renoux, Influence of naloxone on antidepressant drug effects in the forced swimming test in mice, Psychopharmacology 84 (1) (1984) 71–75. S. Ide, S. Fujiwara, M. Fujiwara, I. Sora, K. Ikeda, M. Minami, G.R. Uhl, K. Ishihara, Antidepressant-like effect of venlafaxine is abolished in m-opioid receptor knockout mice, J. Pharmacol. Sci. 114 (1) (2010) 107. M.D.C. de Felipe, I. Jiménez, A. Castro, J. Fuentes, Antidepressant action of imipramine and iprindole in mice is enhanced by inhibitors of enkephalindegrading peptidases, Eur. J. Pharmacol. 159 (2) (1989) 175–180. M.P. Kaster, J. Budni, A.R. Santos, A.L.S. Rodrigues, Pharmacological evidence for the involvement of the opioid system in the antidepressant-like effect of
P. Khaloo et al. / Biomedicine & Pharmacotherapy 83 (2016) 1006–1015
[65]
[66]
[67]
[68]
[69]
[70]
[71]
[72]
[73]
[74]
[75]
[76] [77]
adenosine in the mouse forced swimming test, Eur. J. Pharmacol. 576 (1) (2007) 91–98. P.S. Brocardo, J. Budni, K.R. Lobato, A.R.S. Santos, A.L.S. Rodrigues, Evidence for the involvement of the opioid system in the antidepressant-like effect of folic acid in the mouse forced swimming test, Behav. Brain Res. 200 (1) (2009) 122– 127. A.D. Zomkowski, A.R. Santos, A.L. Rodrigues, Evidence for the involvement of the opioid system in the agmatine antidepressant-like effect in the forced swimming test, Neurosci. Lett. 381 (3) (2005) 279–283. P.S. Naidu, A.H. Lichtman, C.C. Archer, E.L. May, L.S. Harris, M.D. Aceto, NIH 11082 produces anti-depressant-like activity in the mouse tail-suspension test through a delta-opioid receptor mechanism of action, Eur. J. Pharmacol. 566 (1) (2007) 132–136. D.C. Broom, E.M. Jutkiewicz, J.E. Folk, J.R. Traynor, K.C. Rice, J.H. Woods, Nonpeptidic d-opioid receptor agonists reduce immobility in the forced swim assay in rats, Neuropsychopharmacology 26 (6) (2002) 744–755. M.M. Torregrossa, E.M. Jutkiewicz, H.I. Mosberg, G. Balboni, S.J. Watson, J.H. Woods, Peptidic delta opioid receptor agonists produce antidepressant-like effects in the forced swim test and regulate BDNF mRNA expression in rats, Brain Res. 1069 (1) (2006) 172–181. E. Berrocoso, K. Ikeda, I. Sora, G.R. Uhl, P. Sánchez-Blázquez, J.A. Mico, Active behaviours produced by antidepressants and opioids in the mouse tail suspension test, Int. J. Neuropsychopharmacol. 16 (1) (2013) 151–162. M. Rojas-Corrales, E. Berrocoso, J. Gibert-Rahola, J. Mico, Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats, Life Sci. 72 (2) (2002) 143–152. S.D. Mague, A.M. Pliakas, M.S. Todtenkopf, H.C. Tomasiewicz, Y. Zhang, W.C. Stevens, R.M. Jones, P.S. Portoghese, W.A. Carlezon, Antidepressant-like effects of k-opioid receptor antagonists in the forced swim test in rats, J. Pharmacol. Exp. Ther. 305 (1) (2003) 323–330. J.P. McLaughlin, M. Marton-Popovici, C. Chavkin, k Opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses, J. Neurosci. 23 (13) (2003) 5674–5683. J.P. McLaughlin, S. Li, J. Valdez, T.A. Chavkin, C. Chavkin, Social defeat stressinduced behavioral responses are mediated by the endogenous kappa opioid system, Neuropsychopharmacology 31 (6) (2006) 1241–1248. M.R. Bruchas, B.B. Land, M. Aita, M. Xu, S.K. Barot, S. Li, C. Chavkin, Stressinduced p38 mitogen-activated protein kinase activation mediates k-opioiddependent dysphoria, J. Neurosci. 27 (43) (2007) 11614–11623. A.T. Knoll, W.A. Carlezon Jr., Dynorphin, stress, and depression, Brain Res. 1314 (2010) 56–73. S.S. Newton, J. Thome, T.L. Wallace, Y. Shirayama, L. Schlesinger, N. Sakai, J. Chen, R. Neve, E.J. Nestler, R.S. Duman, Inhibition of cAMP response elementbinding protein or dynorphin in the nucleus accumbens produces an antidepressant-like effect, J. Neurosci. 22 (24) (2002) 10883–10890.
1015
[78] P.M. Beardsley, J.L. Howard, K.L. Shelton, F.I. Carroll, Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaineseeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats, Psychopharmacology 183 (1) (2005) 118– 126. [79] J.P. McLaughlin, B.B. Land, S. Li, J.E. Pintar, C. Chavkin, Prior activation of kappa opioid receptors by U50 488 mimics repeated forced swim stress to potentiate cocaine place preference conditioning, Neuropsychopharmacology 31 (4) (2006) 787–794. [80] M. Anjaneyulu, K. Chopra, Possible involvement of cholinergic and opioid receptor mechanisms in fluoxetine mediated antinociception response in streptozotocin-induced diabetic mice, Eur. J. Pharmacol. 538 (1) (2006) 80–84. [81] J. De Gandarias, E. Echevarria, I. Acebes, M. Silio, L. Casis, Effects of imipramine administration on mu-opioid receptor immunostaining in the rat forebrain, Arzneimittel-Forschung 48 (7) (1998) 717–719. [82] A. Dehpour, H. Farsam, M. Azizabadi-Farahani, Inhibition of the morphine withdrawal syndrome and the development of physical dependence by lithium in mice, Neuropharmacology 34 (1) (1995) 115–121. [83] A. Alborzi, S.E. Mehr, F. Rezania, S. Badakhshan, T. Mombeini, H. Shafaroodi, L. Moezi, M.N. Ravan, M. Sharifian, A.R. Dehpour, The effect of lithium chloride on morphine-induced tolerance and dependence in isolated guinea pig ileum, Eur. J. Pharmacol. 545 (2) (2006) 123–128. [84] H. Honar, K. Riazi, H. Homayoun, S. Demehri, M. Dehghani, K. Vafaie, M.R. Ebrahimkhani, N. Rashidi, S.A. Gaskari, A.R. Dehpour, Lithium inhibits the modulatory effects of morphine on susceptibility to pentylenetetrazoleinduced clonic seizure in mice: involvement of a nitric oxide pathway, Brain Res. 1029 (1) (2004) 48–55. [85] A. Dehpour, H. Farsam, M. Azizabadi-Farahani, The effect of lithium on morphine-induced analgesia in mice, Gen. Pharmacol. 25 (8) (1994) 1635– 1641. [86] P. Männistö, L. Saarnivaara, Effect of lithium on the analgesia caused by morphine and two antidepressants in mice, Pharmacology 8 (4–6) (1972) 329– 335. [87] R.B. Raffa, R.P. Martinez, Morphine antinociception is mediated through a LiCl-sensitive, IP3-restorable pathway, Eur. J. Pharmacol. 215 (2–3) (1992) 357–358. [88] R. Raffa, R. Martinez, M. Renzi, E. Codd, LiCl uncouples signal transduction in morphine-induced supraspinal antinociception in mice, Gen. Pharmacol. 26 (2) (1995) 317–320. [89] F. Tulunay, B. Kiran, S. Kaymakcalan, Interaction between morphine and lithium, Acta Med. Turc. 8 (1971) 51–60. [90] S. Amir, Involvement of endogenous opioids with forced swimming-induced immobility in mice, Physiol. Behav. 28 (2) (1982) 249–251. [91] S.P. Sivam, D.R. Smith, K. Takeuchi, J.-S. Hong, Lithium and haloperidol differentially alter the dynorphin A (1–8) and enkephalin levels in the neurointermediate lobe of rat pituitary, Neuropeptides 10 (3) (1987) 291–298.