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Ribeiro DE 1; Casarotto PC 1,2; Biojone C 1,2; Joca SRL 1. ¹ Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil. ² Neuroscience Center, University of Helsinki, Helsinki. There is evidence pointing a potential involvement of P2X7 receptor (P2RX7) in mood disorders. In humans, P2RX7 polymorphism is associated to development of depression (Lucae, S. et al. 2006 ). In animal models, the lack of P2RX7 seems to induce antidepressant-like behavior: P2RX7 KO mice exhibit antidepressant-like phenotype (Basso, A.M. et al. 2009), moreover systemic administration of a Figure 1. Number of escapes (A: t14=2,310), avoidances (B: t14=1,922) and failures (C: t14=2,836) of rats submitted to learned helplessness paradigm and treated with vehicle or imipramine 15 mg/Kg/day during seven days (Student t test; *p<0.05; n=8 animals/group). preferential P2XR antagonist induces antidepressant-like behavior in mice (Pereira, V.S. et al. 2013 ). The aim of this study was to investigate if the behavioral effects induced by classical antidepressant drugs would be associated to decreased expression of P2X7 in the dorsal hippocampus, a brain structure which is crucial to stress Figure 2. Number of escapes (A: t17=2,041), avoidances (B: t17=2,813) and failures (C: t17=3,155) of rats submitted to learned helplessness paradigm and treated with vehicle or desipramine 25 mg/Kg/day during seven days (Student t test; *p<0.05; n=9 -10 animals/group). copying and antidepressant response. Naive 40 inescapable footshocks 0.4mA; 10s; 60±30s intervals Days 1st 2nd 3rd 4th 5th 6th 7th Vehicle Antidepressants drugs: - Imipramine 15 mg/Kg - Desipramine 25mg/Kg Days 1st 2nd 3rd 4th 5th 6th 7th Days 1st 2nd 3rd 4th 5th 6th 7th Figure 3. Stress increased P2X7 receptor in dorsal hippocampus (*p<0.05) and the treatment with imipramine 15mg/Kg/day (F2,18=5,466; **p<0.05), but not with desipramine 25mg/Kg/day (F2,12=4,613; NS), reversed this effect. Statistical analysis: one way ANOVA followed by Newman-Keuls , n= 5-8 animals/group. Our data suggests that the behavioral effects induced by stress are associated to increased expression of P2X7 Quantification of P2X7 receptors from dorsal hippocampus by western blotting 30 escapable footshocks, 0.4mA; 10s; 60±30s intervals; preceded (5s) by a tone receptors in dorsal hippocampus, and imipramine treatment blunted both molecular and behavioral effects of stress. On the other hand, treatment with desipramine only partially attenuated the levels of P2X7 receptors. P.2.a.020 Hippocampal P2X7 receptor expression is modulated by stress and antidepressant treatment in the learned helplessness model D. Ribeiro 1, P.C. Casarotto 2, C. Biojone 2, S.R. Joca 1 1Ribeirao Preto Medical School - University of São Pauloa Pharmacologya Ribeirão Pretoa Brazil 2University of Helsinkia Neuroscience Centera Helsinkia Finland There is evidence pointing a potential involvement of P2X7 receptor aP2RX7) in mood disorders. In humans, P2RX7 polymorphism is associated to development of depression [1]. In animal models, the lack of P2RX7 seems to induce antidepressant-like behavior: P2RX7 KO mice exhibit antidepressant-like phenotype [2], moreover systemic administration of a preferential P2XR antagonist induces antidepressant-like behavior in mice [3]. Therefore, the aim of this study was to investigate if the behavioral effects induced by classical antidepressant drugs would be associated to decreased expression of P2X7 in the hippocampus, a brain structure which is crucial to stress copying and antidepressant response. The learned helplessness model aLH) was used in order to access behavioral effects of antidepressant drugs due its good predictive and face validity. LH is a classical and widely used model of depression based on the observation that exposure to uncontrollable stressors induces behavior deficits. Adult male rats were submitted to LH pre-test session a40 inescapable footshocks: 0.4mA, 10s duration, 30–90s interval) and were treated with vehicle, imipramine 15mg/kg aIMI) or desipramine 25mg/kg aDES) for seven days, and were tested 1 hour after the last injection. The test session consisted of 30 escapable footshocks a0.4mA, 10s duration, 30–90s interval) preceded by a tone a60dB, 670Hz) that started 5s before each shock and lasted until its end. Animals could avoid the shock during sound presentation or interrupt its presentation by crossing to the opposite side of the chamber aescape). Absence of one of these behaviors was considered an escape failure. An independent group of rats was submitted to LH pretest session astressed group) or habituation in the same apparatus anon-stressed group), and then the rats were treated with vehicle, IMI or DES for seven days, and killed 1 hour after the last injection in order to have their dorsal hippocampus dissected. P2RX7 expression in hippocampus was determined by western blotting. IMI at14 = 2.84; p<0.05) or DES at17 = 3.16; p<0.05) treatment decreased the number of escape failures of rats submitted to the LH paradigm. Both, IMI [F 2,20=5.47; p<0.05] and DES [F 2,14=4.61; p<0.05] attenuated the stress-induced P2RX7 expression in the dorsal hippocampus of rats submitted to PT. The post-hoc analysis indicates that IMI-, but not DES-treated animals show significant difference from vehicle-treated groups, but both showed no difference from naïve animals aNewman-Keuls, p<0.05). Our data suggests that the behavioral effects induced by stress are associated to increased expression of P2RX7 in hippocampus, and imipramine treatment blunted both molecular and behavioral effects of stress. On the other hand, treatment with desipramine only partially attenuated the levels of P2X7R. Additional experiments are necessary to elucidate if the differential effects of imipramine and desipramine are related to the preferential effect of this drugs upon serotonergic/noradrenergic signaling. 1. Lucae, S. et al., 2006 P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Human Molecular Genetics 15a16), 2438–2445. 2. Basso, A.M. et al., 2009 Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders. Behavioural Brain Research 198, 83–90. 3. Pereira, V.S. et al., 2013 Antidepressant- and anticompulsive-like effects of purinergic receptor blockade: involvement of nitric oxide. Eur Neuropsychopharmacol 23a12), 1769–1778. Citation: Eur Neuropsychopharmacol. 2014;24aSuppl 2):S372 Keywords Antidepressants: basic Stress Receptors