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P.1.g.027 Effects of traumatic exposure on corticosterone levels and levels after dexamethasone application in rats
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P.1.g. Basic and clinical neuroscience − Neuropharmacology
and returned to control levels between injections. Mephedroneinduced hyperactivity was markedly attenuated (P < 0.05–0.001 for 80 min) and hypothermia completely abolished (P < 0.05–0.01 for 140 min) by prior 5-HT depletion (−35% from control in striatum and −58% in hypothalamus), and mephedrone-induced decreases in rectal temperature were also blocked by 5-HT1A (but not 5-HT7 ) receptor antagonism. In contrast mephedrone-induced hyperactivity was slightly enhanced (P < 0.05 for 20 min) but hypothermia unaffected by dopamine depletion (−48% in striatum, but −15% dopamine and −50% noradrenaline in hypothalamus). This study found no evidence for rapid sensitisation or tolerance to mephedrone during a single binge dosing session. The limited depletion of hypothalamic dopamine makes it impossible to completely exclude a role of this monoamine in mephedroneinduced hypothermia. However, since this response is unaffected by D2 receptor blockade and prolonged by D1 receptor antagonism [3] the available evidence suggests mephedrone-induced increases in dopamine efflux are unlikely to contribute to the drug-induced hypothermia. In contrast, modulation of central serotonergic neurotransmission plays a key role in mediating both the hyperlocomotor and hypothermic effects of mephedrone. Although 5-HT1A receptors are implicated in the hypothermic response their involvement is almost certainly a consequence of 5-HT release and/or inhibition of reuptake, since the low affinity of mephedrone for the 5-HT1A receptor (Ki>20mM; [1]) makes any direct effect unlikely. References [1] Simmler, L.D., Buser, T.A., Donzelli, M., Schramm, Y., Dieu, L.H., Huwyler, J., Chaboz, S., Hoener, M.C., Liechti, M.E., 2013 Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol. 168, 458–470. [2] Parrott, A.C., 2005 Chronic tolerance to recreational MDMA (3,4methylenedioxymethamphetamine) or Ecstasy. J Psychopharmacol. 19, 71−83. [3] Shortall, S.E., Green, A.R., Swift, K.M., Fone, K.C., King, M.V., 2013 Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia. Br J Pharmacol. 168, 966–977. Disclosure statement: This work was funded by the University of Nottingham.
P.1.g.027 Effects of traumatic exposure on corticosterone levels and levels after dexamethasone application in rats A. Starcevic1 ° , S. Petricevic1 , Z. Radojicic2 , B. Starcevic3 , S. Dencic4 , Z. Stanojevic4 , B. Filipovic5 1 Institute of Anatomy Niko Miljanic Medical faculty University of Belgrade, Neuroanatomy, Belgrade, Serbia; 2 Statistics, Belgrade, Serbia; 3 Orthopaedics, Neuroorthopaedics, Belgrade, Serbia; 4 Institute for biochemistry, Belgrade, Serbia; 5 Institute for Anatomy, neuroanatomy, Belgrade, Serbia Purpose of the study was to investigate the effects of combined predator stress exposure and daily stress instability on levels of corticosterone and levels following the administration of dexamethasone on animal model of posttraumatic stress disorder. Methods: Adult male Wistar albino rats were used for the experiment. After a two weeks period of acclimatization, the animals were divided in two groups. The experimental group was scheduled to exposure to two types of stressors: double exposure to acute immobilization stress and combined predator
threat stress and daily social stress. There was also administration of dexamethasone in combination with stress exposure. Blood samples of all animals were taken 25 days after the exposure to the second acute stress according to the following procedure: blood samples were first taken from the animals before exposure to the stress by placing the animals into plastic immobilization tubes for 20 minutes. Blood from those animals were sampled again after they had been released from the immobilization tubes and the animals were placed into cages to rest. Blood was sampled for the third time two hours after animal release from the immobilization tubes. The blood samples were taken from the sublingual vein and tthe serum sample was tested for corticosterone levels [1,2]. The animals were sacrificed after the third blood sampling by capitation. The thymuses were isolated and weighed. Results: We used descriptive and exploratory analysis for statistical assesmant. There was a difference in the weight of thymus F = 4.336; p = 0.048 when we used Fisher F test. Statistically significant difference between the mass of the thymus in the stress group and stress group with dexamethasone administration (p = 0.024) was found in the case of thymus mass when we used LSD test. There was no statistical significance in the interaction in the group of the dexamethasone administration and the stress group (p > 0.05). Repeated measure ANOVA was used to analyse the corticosterone levels between times measuring in each groups and showed statistically significant effect (F = 30.762; p < 0.001). Pairwise comparation between different time measuring we used LSD test and found statistical significance between baseline corticosterone levels and stress inducedlevels of corticosterone (p < 0.001) and between stress induced group and return to baseline group (p = 0.022). There were no statistically significant differences in the level of corticosterone in the group of dexamethasone. Conclusions: Posttraumatic stress disorder is a condition that can develop in anyone who was exposed to some traumatic experience and many studies in the field of posttraumatic stress disorder indicate that glucocorticoid levels are decreased. Psychosocially stressed rats exhibited significantly smaller thymuses and reduction in growth rate compared to control rats. Rats exposed to chronic psychosocial stress exhibited significantly lower baseline levels of corticosterone than control animals. Development of appropriate animal models is critical for studying morphological and pathophysiological supstrates and mechanisms tah underlie the formation and persistence of nowdays global problem of posttraumatic stress disorder psychopathology. References [1] Zoladz PR, Conrad CD, Fleshner M, Diamond DM. Acute episodes of predator exposure in conjuction with chronic social instability as an animal model of posttraumatic stress disorder. Stress. 2008; 11: 259– 281. [2] Zohar J, Matar MA., Ifergane G., Kaplan Z., Cohen H. Brief posttraumatic stressor treatment with pregabalin in an animal model for PTSD: Short term anxiolytic effects without long term anxiogenic effect. Eur Neuropsychopharmacol. 2008; 18: 653–666.
P.1.g. Basic and clinical neuroscience − Neuropharmacology
and returned to control levels between injections. Mephedroneinduced hyperactivity was markedly attenuated (P < 0.05–0.001 for 80 min) and hypothermia completely abolished (P < 0.05–0.01 for 140 min) by prior 5-HT depletion (−35% from control in striatum and −58% in hypothalamus), and mephedrone-induced decreases in rectal temperature were also blocked by 5-HT1A (but not 5-HT7 ) receptor antagonism. In contrast mephedrone-induced hyperactivity was slightly enhanced (P < 0.05 for 20 min) but hypothermia unaffected by dopamine depletion (−48% in striatum, but −15% dopamine and −50% noradrenaline in hypothalamus). This study found no evidence for rapid sensitisation or tolerance to mephedrone during a single binge dosing session. The limited depletion of hypothalamic dopamine makes it impossible to completely exclude a role of this monoamine in mephedroneinduced hypothermia. However, since this response is unaffected by D2 receptor blockade and prolonged by D1 receptor antagonism [3] the available evidence suggests mephedrone-induced increases in dopamine efflux are unlikely to contribute to the drug-induced hypothermia. In contrast, modulation of central serotonergic neurotransmission plays a key role in mediating both the hyperlocomotor and hypothermic effects of mephedrone. Although 5-HT1A receptors are implicated in the hypothermic response their involvement is almost certainly a consequence of 5-HT release and/or inhibition of reuptake, since the low affinity of mephedrone for the 5-HT1A receptor (Ki>20mM; [1]) makes any direct effect unlikely. References [1] Simmler, L.D., Buser, T.A., Donzelli, M., Schramm, Y., Dieu, L.H., Huwyler, J., Chaboz, S., Hoener, M.C., Liechti, M.E., 2013 Pharmacological characterization of designer cathinones in vitro. Br J Pharmacol. 168, 458–470. [2] Parrott, A.C., 2005 Chronic tolerance to recreational MDMA (3,4methylenedioxymethamphetamine) or Ecstasy. J Psychopharmacol. 19, 71−83. [3] Shortall, S.E., Green, A.R., Swift, K.M., Fone, K.C., King, M.V., 2013 Differential effects of cathinone compounds and MDMA on body temperature in the rat, and pharmacological characterization of mephedrone-induced hypothermia. Br J Pharmacol. 168, 966–977. Disclosure statement: This work was funded by the University of Nottingham.
P.1.g.027 Effects of traumatic exposure on corticosterone levels and levels after dexamethasone application in rats A. Starcevic1 ° , S. Petricevic1 , Z. Radojicic2 , B. Starcevic3 , S. Dencic4 , Z. Stanojevic4 , B. Filipovic5 1 Institute of Anatomy Niko Miljanic Medical faculty University of Belgrade, Neuroanatomy, Belgrade, Serbia; 2 Statistics, Belgrade, Serbia; 3 Orthopaedics, Neuroorthopaedics, Belgrade, Serbia; 4 Institute for biochemistry, Belgrade, Serbia; 5 Institute for Anatomy, neuroanatomy, Belgrade, Serbia Purpose of the study was to investigate the effects of combined predator stress exposure and daily stress instability on levels of corticosterone and levels following the administration of dexamethasone on animal model of posttraumatic stress disorder. Methods: Adult male Wistar albino rats were used for the experiment. After a two weeks period of acclimatization, the animals were divided in two groups. The experimental group was scheduled to exposure to two types of stressors: double exposure to acute immobilization stress and combined predator
threat stress and daily social stress. There was also administration of dexamethasone in combination with stress exposure. Blood samples of all animals were taken 25 days after the exposure to the second acute stress according to the following procedure: blood samples were first taken from the animals before exposure to the stress by placing the animals into plastic immobilization tubes for 20 minutes. Blood from those animals were sampled again after they had been released from the immobilization tubes and the animals were placed into cages to rest. Blood was sampled for the third time two hours after animal release from the immobilization tubes. The blood samples were taken from the sublingual vein and tthe serum sample was tested for corticosterone levels [1,2]. The animals were sacrificed after the third blood sampling by capitation. The thymuses were isolated and weighed. Results: We used descriptive and exploratory analysis for statistical assesmant. There was a difference in the weight of thymus F = 4.336; p = 0.048 when we used Fisher F test. Statistically significant difference between the mass of the thymus in the stress group and stress group with dexamethasone administration (p = 0.024) was found in the case of thymus mass when we used LSD test. There was no statistical significance in the interaction in the group of the dexamethasone administration and the stress group (p > 0.05). Repeated measure ANOVA was used to analyse the corticosterone levels between times measuring in each groups and showed statistically significant effect (F = 30.762; p < 0.001). Pairwise comparation between different time measuring we used LSD test and found statistical significance between baseline corticosterone levels and stress inducedlevels of corticosterone (p < 0.001) and between stress induced group and return to baseline group (p = 0.022). There were no statistically significant differences in the level of corticosterone in the group of dexamethasone. Conclusions: Posttraumatic stress disorder is a condition that can develop in anyone who was exposed to some traumatic experience and many studies in the field of posttraumatic stress disorder indicate that glucocorticoid levels are decreased. Psychosocially stressed rats exhibited significantly smaller thymuses and reduction in growth rate compared to control rats. Rats exposed to chronic psychosocial stress exhibited significantly lower baseline levels of corticosterone than control animals. Development of appropriate animal models is critical for studying morphological and pathophysiological supstrates and mechanisms tah underlie the formation and persistence of nowdays global problem of posttraumatic stress disorder psychopathology. References [1] Zoladz PR, Conrad CD, Fleshner M, Diamond DM. Acute episodes of predator exposure in conjuction with chronic social instability as an animal model of posttraumatic stress disorder. Stress. 2008; 11: 259– 281. [2] Zohar J, Matar MA., Ifergane G., Kaplan Z., Cohen H. Brief posttraumatic stressor treatment with pregabalin in an animal model for PTSD: Short term anxiolytic effects without long term anxiogenic effect. Eur Neuropsychopharmacol. 2008; 18: 653–666.