- Email: [email protected]
healthy rats
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P.1.h. Basic and clinical neuroscience − Animal behaviour
ASD. In particular, we observed altered social behavior in VPAexposed rats both during adolescence and adulthood. Furthermore, the altered activation of CB1 receptors in different brain areas involved in socio-emotional functioning, together with the positive effect of pharmacological manipulation of the endocannabinoid system, suggests a possible involvement of the endocannabinoid system in the symptomatology and etiology of ASD. References [1] Schneider, T., Przewlocki, R., 2005. Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology 30(1), 80−9.
P.1.h.004 A new model of impulsivity, social interactions and preference of alcohol in mice living in groups L. Szumiec1 ° , J. Rodriguez-Parkitna1 1 Institute of Pharmacology- Polish Academy of Sciences, Molecular Pharmacology, Krak´ow, Poland Background: Impulsive behaviour is an important component of clinical symptoms in several psychiatric disorders. Inability to tolerate a delay of grafitication is one important factor which might lead to aggression, frustration or violence [2,3]. The goal of our project is identification of neuronal mechanisms responsible for economic decision making. We have developed a set of new models that assess the effects of delay on choice behavior. The rationale for the development of novel models was to test behaviors under minimal environmental constraints, as similar to natural conditions as possible [1]. Methods: We have worked on model of testing delay discounting in mice living in groups. A cohort of 10−16 mice was implanted subcutaneously with radiofrequency identification chips and placed into a cage equipped with sensors for automatic tracking and 4 corners with 2 drinking bottles for each accessed through a small compartment (Intellicage Plus). Mice can be individually monitored and restricted to model effects of delay discounting. Results: Two models were tested: choice between saccharin and water and choice among two concentrations of saccharin (0.01%, 0.1%) and water. The former is simpler, while the latter allows for comparison of the same reward with different magnitudes. In both models mice showed initially high preference for 0.1% sachharin and shifted preference towards water or 0.01% saccharin when the delay reached more than 8s. To validate the model we have tested the effects of an irreversible inhibitor of the monoamine oxidase − tranylcypromine (3 mg/kg ip., single injection) on delay discounting. In line with expectations the drug induced increase in monoamine levels caused acceleration of delay discounting (t-test with Bonferroni, p(14s.) = 0.04; p(17s.) = 0.02; p(20s) = 0.006). Also we have tested cloccinamox (10 mg/kg ip.), an opioid receptor antagonist but it hadn’t effect on delay discounting (t-test with Bonferroni, p = 0.35) We have tested also the preference of saccharin and the most important parameter called the indifference point, which represents the value of the delayed outcome. It is exactly when the preference between values is equal (in our case is about 17s of delay on the greater one). Furthermore, we have tested an example of social interactions with following (5 pairs of mice: leader/follower). Mice would get a reward only if had entered to corner after suitable leader. Followers could follow their leaders to get a reward (preference even 50%). Moreover, we have
tested the preference of drinking alcohol (4, 8, 12%), as alleged the preference decreased steeply from 0.70 (4%), 0.46 (8%) and 0.11 (12%). Conclusions: The main advantages of the new model are the ability to test behaviour in the home cage in group housed mice, during natural activity cycles, no interaction with the experimenter and without pharmacological treatments or genetic modifications on delay discounting. The further research will be based on social interactions and ADE (model of alcoholism). References [1] Parkitna, J.R., Sikora, M., Gołda, S., Gołembiowska, K., Bystrowska, B., Engblom, D., Bilbao, A., Przewlocki, R., 2013. Novelty-seeking behaviors and the escalation of alcohol drinking after abstinence in mice are controlled by metabotropic glutamate receptor 5 on neurons expressing dopamine d1 receptors. Biological Psychiatry 73(3), 263−27. [2] Yates, J.R., Batten, S.R., Bardo, M.T., Beckmann, J.S., 2015. Role of ionotropic glutamate receptors in delay and probability discounting in the rat. Psychopharmacology 232(7), 1187–119. [3] Evenden, J.L., Ryan, C.N., 1996. The pharmacology of impulsive behaviour in rats: the effects of drugs on response choice with varying delays of reinforcement. Psychopharmacology 128(2), 161–170.
P.1.h.005 Anxiolytic-like effect of gallic acid and quercetin in young/healthy rats A. Georgieva1 ° , I. Belcheva2 , S. Belcheva3 , R. Tashev4 , S. Valcheva-Kuzmanova1 1 Medical University “Prof. Dr. Paraskev Stoyanov”, Preclinical and Clinical Pharmacology, Varna, Bulgaria; 2 Institute of Neurobiology- Bulgarian Academy of Sciences- Sofia- Bulgaria, Behavioral neurobiology, Sofia, Bulgaria; 3 Sofia University, Department of Pre-school and Primary School Education, Sofia, Bulgaria; 4 Medical universitySofia, Pathophysiology, Sofia, Bulgaria Introduction: Some of the most widespread polyphenols in natural food sources are phenolic acids such as gallic acid and flavonoids such as quercetin. An anxiolytic-like effect of gallic acid was observed after a single intraperitoneal administration [1]. There are some data suggesting an anxiolytic-like effect of quercetin given as a single dose [2], and repeatedly at a high dose [3]. Aim: The aim of the present study was to investigate the effect of gallic acid and quercetin administered subchronically at equal low doses on anxiety in young/healthy rats. Methods: Male Wistar rats (200–250 g) were used in the experiments. The treatment lasted for 7, 14, 21 or 30 days. For each treatment period, there were three groups receiving daily orally one of the following treatments: saline 10 ml/kg (controls), gallic acid (20 mg/kg as a 10 ml/kg solution) or quercetin (20 mg/kg as a 10 ml/kg solution). After each treatment period, animals were tested in the elevated plus-maze which is a common test for anxiety behavior in rodents. Its concept lies in the conflict between the natural fear of the animals from open areas and their curiosity to a novel environment [4]. The test was carried out on 12 different animal groups (3 kinds of treatment, 4 treatment durations) consisting of 10 rats each. The following indices were recorded during the 5-min test period: the number of entries into open arms and the time spent there, the number of entries into closed arms of the maze and the time spent there, the total number of arm entries, and the ratio of the number of entries into the open arms vs. total number of entries. The statistical analyses were performed by one-way ANOVA using GraphPad Prism statistical software. Results: Applied for 7 days, gallic acid and quercetin had no significant effects on the recorded indices. The two kinds
P.1.h. Basic and clinical neuroscience − Animal behaviour of treatment administered for 14, 21 and 30 days significantly increased the number of entries in the open arms of the plus-maze and prolonged the time spent there without a significant change in the total number of arm entries serving as a measure of the animal locomotor activity. After the same treatment periods, the two phenolic substances had no effect on the number of entries into the closed arms but significantly shortened the time spent there. When applied for 14 and 30 days, gallic acid and quercetin increased the ratio of open vs. total arm entries. The onset of the effects after 14 days might be explained with the cumulation of polyphenolic substances in the brain after a long-term consumption [5]. Conclusion: The increased number of entries into plus-maze open arms together with no change in the overall locomotor activity, as well as the increased open-arm time and the decreased closed-arm time suggest a comparable anxiolytic-like effect of the equal low doses of gallic acid and quercetin. References [1] Mansouri, M.T., Soltani, M., Naghizadeh, B., Farbood, Y., Mashak, A., Sarkaki, A., 2014. A possible mechanism for the anxiolytic-like effect of gallic acid in the rat elevated plus maze. Pharmacol Biochem Behav 117, 40−46. [2] Bhutada, P., Mundhada, Y., Bansod, K., Ubgade, A., Quazi, M., Umathe, S., Mundhadaa, D., 2010. Reversal by quercetin of corticotrophin releasing factor induced anxiety- and depression-like effect in mice. Progr Neuropsychopharmacol Biol Psychiatry 34(6), 955–960. [3] Priprem, A., Watanatorn, J., Sutthiparinyanont, S., Phachonpai, W., Muchimapura, S., 2008. Anxiety and cognitive effects of quercetin liposomes in rats. Nanomed Nanotechnol Biol Med 4, 70−78. [4] Pellow, S., File, S., 1986. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: A novel test of anxiety in the rat. Pharmacol Biochem Behav 24(3), 525–529. [5] Willis, L.M., Shukitt-Hale, B., Joseph, J.A., 2009. Recent advances in berry supplementation and age-related cognitive decline. Curr Opin Clin Nutr Metab Care 12(1), 91−94.
P.1.h.006 Experimental study of the antinociceptive properties of the antidepressant escitalopram in animal models of acute pain H. Zlatanova1 ° , I. Kandilarov1 , I. Kostadinov1 , D. Delev1 , I. Kostadinova1 1 Medical University Plovdiv, Pharmacology and clinical pharmacology, Plovdiv, Bulgaria Background: Antidepressants are medications used in the therapy of depression and anxiety disorders. They have been found to possess antinociceptive and analgesic properties in chronic pain conditions [1]. The mechanisms responsible for these effects are not entirely clear. It has been hypothesized they result from inhibition of reuptake of serotonin and norepinephrine. It is known that bulbospinal and supraspinal monoaminergic pathways have a role in the descending modulation of pain transmission and behavioral expression of pain, respectively [2]. Escitalopram is an antidepressant from the group of SSRIs. Studies on mice showed that it does not possess antinociceptive properties after single administration [3], but some clinical trials found pain-relieving effects of this antidepressant [4]. The aim of this study was to evaluate the possible antinociceptive properties of the SSRI escitalopram after multiple administration (14 days) using animal pain models. Methods: Forty adult male Wistar rats were used, divided in 5 groups (n = 8). The animals were treated with saline (control group), metamizole 150 mg/kg b.w., escitalopram 5, 10 and 20 mg/kg b.w. intraperitoneally. The nociceptive tests used employ thermal (hot plate and plantar test), mechanical (paw pressure) and chemical (formalin test) stimuli. Criteria for analgesic effect
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were increased latency in hot plate, paw pressure and plantar test, and decreased hind paw licking time in formalin test. Statistical evaluation of the results was performed with SPSS computer program. For each indicator were determined arithmetic mean and standard error (±SEM). Comparison of the results between groups was done using the Independent Sample T test. A P value <0.05 was considered statistically significant. Results: The reference analgesic metamizole showed significant analgesic effect in all tests excluding both phases of formalin. Escitalopram in dose 10 mg/kg b.w. increased the latency in paw pressure test at the second and third hour compared to the control. Escitalopram 10 mg/kg b.w. prolonged the stay on the hot plate at the first, second and third hours, while dose 20 mg/kg b.w. significantly increased this indicator at the first and second hours in comparison to the group, treated with saline. In the plantar test, escitalopram in all used doses significantly increased the nociceptive response latency at all tested hours compared to the control animals. As the behavior reflex responses in hot plate and plantar test are mediated through supraspinal structures we can speculate that supraspinal serotonergic pathways are involved in escitalopram-induced analgesia. Doses 10 and 20 mg/kg b.w. decreased second phase hind paw licking in the formalin test compared to the control group. This phase is attributed not only to peripheral inflammatory processes but also to subsequent sensitization of nociceptive spinal neurons; therefore our results indicate that spinal pathways are also implicated in the mode of antinociceptive action of escitalopram. Conclusion: Escitalopram induces antinociceptive effect after repeated administration in rats, and this effect is probably mediated through supraspinal and spinal serotonergic pathways. The observed effect is not dose dependent and the most sensitive model for studying it is the plantar test where all used doses showed significant analgesic action. References [1] Mika J., Zychowska M., Makuch W., Rojewska E., Przewlocka B., 2013. Neuronal and immunological basis of action of antidepressants in chronic pain − clinical and experimental studies. Pharmacological Reports 65, 1611–1621. [2] Rosenberg M. B., Carroll F. I., Negus S. S., 2013. Effects of monoamine reuptake inhibitors in assays of acute pain-stimulated and pain-depressed behavior in rats. The Journal of Pain 14 (3), 246–259. [3] Schreiber S., Pick C. G., 2006. From selective to highly selective SSRIs: A comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram. European Neuropsychopharmacology 16, 464–468. [4] Jaracz J., Gattner K., Moczko J., Hauser J., 2015. Comparison of the effects of escitalopram and nortriptyline on painful symptoms in patients with major depression. General Hospital Psychiatry 37, 36−39.
P.1.h.007 Peripheral immunization of mice to produce antibodies against NMDA receptor as a potential approach to create a rodent model of schizophrenia L. Mus1 ° , S. Espinoza2 , G. Ronzitti3 , F. Mingozzi3 , R.R. Gainetdinov4 1 Pavlov Saint Petersburg First State Medical University, Dept of Psychopharmacology, Saint Petersburg, Russia; 2 Istituto Italiano di Tecnologia, Department of Neuroscience and Brain Technologies, Genoa, Italy; 3 Genethon, Gene therapy, Evry, France; 4 St. Petersburg State University, Institute of Translational Biomedicine, Saint Petersburg, Russia Background: Anti-NMDA receptor encephalitis is a potentially lethal autoimmune disease characterized by production of antibodies against N-terminal domain of GluN1 subunit of NMDA
P.1.h. Basic and clinical neuroscience − Animal behaviour
ASD. In particular, we observed altered social behavior in VPAexposed rats both during adolescence and adulthood. Furthermore, the altered activation of CB1 receptors in different brain areas involved in socio-emotional functioning, together with the positive effect of pharmacological manipulation of the endocannabinoid system, suggests a possible involvement of the endocannabinoid system in the symptomatology and etiology of ASD. References [1] Schneider, T., Przewlocki, R., 2005. Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism. Neuropsychopharmacology 30(1), 80−9.
P.1.h.004 A new model of impulsivity, social interactions and preference of alcohol in mice living in groups L. Szumiec1 ° , J. Rodriguez-Parkitna1 1 Institute of Pharmacology- Polish Academy of Sciences, Molecular Pharmacology, Krak´ow, Poland Background: Impulsive behaviour is an important component of clinical symptoms in several psychiatric disorders. Inability to tolerate a delay of grafitication is one important factor which might lead to aggression, frustration or violence [2,3]. The goal of our project is identification of neuronal mechanisms responsible for economic decision making. We have developed a set of new models that assess the effects of delay on choice behavior. The rationale for the development of novel models was to test behaviors under minimal environmental constraints, as similar to natural conditions as possible [1]. Methods: We have worked on model of testing delay discounting in mice living in groups. A cohort of 10−16 mice was implanted subcutaneously with radiofrequency identification chips and placed into a cage equipped with sensors for automatic tracking and 4 corners with 2 drinking bottles for each accessed through a small compartment (Intellicage Plus). Mice can be individually monitored and restricted to model effects of delay discounting. Results: Two models were tested: choice between saccharin and water and choice among two concentrations of saccharin (0.01%, 0.1%) and water. The former is simpler, while the latter allows for comparison of the same reward with different magnitudes. In both models mice showed initially high preference for 0.1% sachharin and shifted preference towards water or 0.01% saccharin when the delay reached more than 8s. To validate the model we have tested the effects of an irreversible inhibitor of the monoamine oxidase − tranylcypromine (3 mg/kg ip., single injection) on delay discounting. In line with expectations the drug induced increase in monoamine levels caused acceleration of delay discounting (t-test with Bonferroni, p(14s.) = 0.04; p(17s.) = 0.02; p(20s) = 0.006). Also we have tested cloccinamox (10 mg/kg ip.), an opioid receptor antagonist but it hadn’t effect on delay discounting (t-test with Bonferroni, p = 0.35) We have tested also the preference of saccharin and the most important parameter called the indifference point, which represents the value of the delayed outcome. It is exactly when the preference between values is equal (in our case is about 17s of delay on the greater one). Furthermore, we have tested an example of social interactions with following (5 pairs of mice: leader/follower). Mice would get a reward only if had entered to corner after suitable leader. Followers could follow their leaders to get a reward (preference even 50%). Moreover, we have
tested the preference of drinking alcohol (4, 8, 12%), as alleged the preference decreased steeply from 0.70 (4%), 0.46 (8%) and 0.11 (12%). Conclusions: The main advantages of the new model are the ability to test behaviour in the home cage in group housed mice, during natural activity cycles, no interaction with the experimenter and without pharmacological treatments or genetic modifications on delay discounting. The further research will be based on social interactions and ADE (model of alcoholism). References [1] Parkitna, J.R., Sikora, M., Gołda, S., Gołembiowska, K., Bystrowska, B., Engblom, D., Bilbao, A., Przewlocki, R., 2013. Novelty-seeking behaviors and the escalation of alcohol drinking after abstinence in mice are controlled by metabotropic glutamate receptor 5 on neurons expressing dopamine d1 receptors. Biological Psychiatry 73(3), 263−27. [2] Yates, J.R., Batten, S.R., Bardo, M.T., Beckmann, J.S., 2015. Role of ionotropic glutamate receptors in delay and probability discounting in the rat. Psychopharmacology 232(7), 1187–119. [3] Evenden, J.L., Ryan, C.N., 1996. The pharmacology of impulsive behaviour in rats: the effects of drugs on response choice with varying delays of reinforcement. Psychopharmacology 128(2), 161–170.
P.1.h.005 Anxiolytic-like effect of gallic acid and quercetin in young/healthy rats A. Georgieva1 ° , I. Belcheva2 , S. Belcheva3 , R. Tashev4 , S. Valcheva-Kuzmanova1 1 Medical University “Prof. Dr. Paraskev Stoyanov”, Preclinical and Clinical Pharmacology, Varna, Bulgaria; 2 Institute of Neurobiology- Bulgarian Academy of Sciences- Sofia- Bulgaria, Behavioral neurobiology, Sofia, Bulgaria; 3 Sofia University, Department of Pre-school and Primary School Education, Sofia, Bulgaria; 4 Medical universitySofia, Pathophysiology, Sofia, Bulgaria Introduction: Some of the most widespread polyphenols in natural food sources are phenolic acids such as gallic acid and flavonoids such as quercetin. An anxiolytic-like effect of gallic acid was observed after a single intraperitoneal administration [1]. There are some data suggesting an anxiolytic-like effect of quercetin given as a single dose [2], and repeatedly at a high dose [3]. Aim: The aim of the present study was to investigate the effect of gallic acid and quercetin administered subchronically at equal low doses on anxiety in young/healthy rats. Methods: Male Wistar rats (200–250 g) were used in the experiments. The treatment lasted for 7, 14, 21 or 30 days. For each treatment period, there were three groups receiving daily orally one of the following treatments: saline 10 ml/kg (controls), gallic acid (20 mg/kg as a 10 ml/kg solution) or quercetin (20 mg/kg as a 10 ml/kg solution). After each treatment period, animals were tested in the elevated plus-maze which is a common test for anxiety behavior in rodents. Its concept lies in the conflict between the natural fear of the animals from open areas and their curiosity to a novel environment [4]. The test was carried out on 12 different animal groups (3 kinds of treatment, 4 treatment durations) consisting of 10 rats each. The following indices were recorded during the 5-min test period: the number of entries into open arms and the time spent there, the number of entries into closed arms of the maze and the time spent there, the total number of arm entries, and the ratio of the number of entries into the open arms vs. total number of entries. The statistical analyses were performed by one-way ANOVA using GraphPad Prism statistical software. Results: Applied for 7 days, gallic acid and quercetin had no significant effects on the recorded indices. The two kinds
P.1.h. Basic and clinical neuroscience − Animal behaviour of treatment administered for 14, 21 and 30 days significantly increased the number of entries in the open arms of the plus-maze and prolonged the time spent there without a significant change in the total number of arm entries serving as a measure of the animal locomotor activity. After the same treatment periods, the two phenolic substances had no effect on the number of entries into the closed arms but significantly shortened the time spent there. When applied for 14 and 30 days, gallic acid and quercetin increased the ratio of open vs. total arm entries. The onset of the effects after 14 days might be explained with the cumulation of polyphenolic substances in the brain after a long-term consumption [5]. Conclusion: The increased number of entries into plus-maze open arms together with no change in the overall locomotor activity, as well as the increased open-arm time and the decreased closed-arm time suggest a comparable anxiolytic-like effect of the equal low doses of gallic acid and quercetin. References [1] Mansouri, M.T., Soltani, M., Naghizadeh, B., Farbood, Y., Mashak, A., Sarkaki, A., 2014. A possible mechanism for the anxiolytic-like effect of gallic acid in the rat elevated plus maze. Pharmacol Biochem Behav 117, 40−46. [2] Bhutada, P., Mundhada, Y., Bansod, K., Ubgade, A., Quazi, M., Umathe, S., Mundhadaa, D., 2010. Reversal by quercetin of corticotrophin releasing factor induced anxiety- and depression-like effect in mice. Progr Neuropsychopharmacol Biol Psychiatry 34(6), 955–960. [3] Priprem, A., Watanatorn, J., Sutthiparinyanont, S., Phachonpai, W., Muchimapura, S., 2008. Anxiety and cognitive effects of quercetin liposomes in rats. Nanomed Nanotechnol Biol Med 4, 70−78. [4] Pellow, S., File, S., 1986. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: A novel test of anxiety in the rat. Pharmacol Biochem Behav 24(3), 525–529. [5] Willis, L.M., Shukitt-Hale, B., Joseph, J.A., 2009. Recent advances in berry supplementation and age-related cognitive decline. Curr Opin Clin Nutr Metab Care 12(1), 91−94.
P.1.h.006 Experimental study of the antinociceptive properties of the antidepressant escitalopram in animal models of acute pain H. Zlatanova1 ° , I. Kandilarov1 , I. Kostadinov1 , D. Delev1 , I. Kostadinova1 1 Medical University Plovdiv, Pharmacology and clinical pharmacology, Plovdiv, Bulgaria Background: Antidepressants are medications used in the therapy of depression and anxiety disorders. They have been found to possess antinociceptive and analgesic properties in chronic pain conditions [1]. The mechanisms responsible for these effects are not entirely clear. It has been hypothesized they result from inhibition of reuptake of serotonin and norepinephrine. It is known that bulbospinal and supraspinal monoaminergic pathways have a role in the descending modulation of pain transmission and behavioral expression of pain, respectively [2]. Escitalopram is an antidepressant from the group of SSRIs. Studies on mice showed that it does not possess antinociceptive properties after single administration [3], but some clinical trials found pain-relieving effects of this antidepressant [4]. The aim of this study was to evaluate the possible antinociceptive properties of the SSRI escitalopram after multiple administration (14 days) using animal pain models. Methods: Forty adult male Wistar rats were used, divided in 5 groups (n = 8). The animals were treated with saline (control group), metamizole 150 mg/kg b.w., escitalopram 5, 10 and 20 mg/kg b.w. intraperitoneally. The nociceptive tests used employ thermal (hot plate and plantar test), mechanical (paw pressure) and chemical (formalin test) stimuli. Criteria for analgesic effect
S271
were increased latency in hot plate, paw pressure and plantar test, and decreased hind paw licking time in formalin test. Statistical evaluation of the results was performed with SPSS computer program. For each indicator were determined arithmetic mean and standard error (±SEM). Comparison of the results between groups was done using the Independent Sample T test. A P value <0.05 was considered statistically significant. Results: The reference analgesic metamizole showed significant analgesic effect in all tests excluding both phases of formalin. Escitalopram in dose 10 mg/kg b.w. increased the latency in paw pressure test at the second and third hour compared to the control. Escitalopram 10 mg/kg b.w. prolonged the stay on the hot plate at the first, second and third hours, while dose 20 mg/kg b.w. significantly increased this indicator at the first and second hours in comparison to the group, treated with saline. In the plantar test, escitalopram in all used doses significantly increased the nociceptive response latency at all tested hours compared to the control animals. As the behavior reflex responses in hot plate and plantar test are mediated through supraspinal structures we can speculate that supraspinal serotonergic pathways are involved in escitalopram-induced analgesia. Doses 10 and 20 mg/kg b.w. decreased second phase hind paw licking in the formalin test compared to the control group. This phase is attributed not only to peripheral inflammatory processes but also to subsequent sensitization of nociceptive spinal neurons; therefore our results indicate that spinal pathways are also implicated in the mode of antinociceptive action of escitalopram. Conclusion: Escitalopram induces antinociceptive effect after repeated administration in rats, and this effect is probably mediated through supraspinal and spinal serotonergic pathways. The observed effect is not dose dependent and the most sensitive model for studying it is the plantar test where all used doses showed significant analgesic action. References [1] Mika J., Zychowska M., Makuch W., Rojewska E., Przewlocka B., 2013. Neuronal and immunological basis of action of antidepressants in chronic pain − clinical and experimental studies. Pharmacological Reports 65, 1611–1621. [2] Rosenberg M. B., Carroll F. I., Negus S. S., 2013. Effects of monoamine reuptake inhibitors in assays of acute pain-stimulated and pain-depressed behavior in rats. The Journal of Pain 14 (3), 246–259. [3] Schreiber S., Pick C. G., 2006. From selective to highly selective SSRIs: A comparison of the antinociceptive properties of fluoxetine, fluvoxamine, citalopram and escitalopram. European Neuropsychopharmacology 16, 464–468. [4] Jaracz J., Gattner K., Moczko J., Hauser J., 2015. Comparison of the effects of escitalopram and nortriptyline on painful symptoms in patients with major depression. General Hospital Psychiatry 37, 36−39.
P.1.h.007 Peripheral immunization of mice to produce antibodies against NMDA receptor as a potential approach to create a rodent model of schizophrenia L. Mus1 ° , S. Espinoza2 , G. Ronzitti3 , F. Mingozzi3 , R.R. Gainetdinov4 1 Pavlov Saint Petersburg First State Medical University, Dept of Psychopharmacology, Saint Petersburg, Russia; 2 Istituto Italiano di Tecnologia, Department of Neuroscience and Brain Technologies, Genoa, Italy; 3 Genethon, Gene therapy, Evry, France; 4 St. Petersburg State University, Institute of Translational Biomedicine, Saint Petersburg, Russia Background: Anti-NMDA receptor encephalitis is a potentially lethal autoimmune disease characterized by production of antibodies against N-terminal domain of GluN1 subunit of NMDA