Nmda Receptors Are Involved in the Antidepressant-Like Effects of Capsaicin Following Amphetamine Withdrawal in Male Mice Publisher Pubmed



Amiri S^{1, 2} ; Alijanpour S³ ; Tirgar F⁴ ; Hajmirzaian A^{1, 5} ; Aminikhoei H^{1, 5} ; Rahimibalaei M⁶ ; Rastegar M² ; Ghaderi M⁴ ; Ghazikhansari M^{1, 5} ; Zarrindast MR^{1, 7, 8} Show Affiliations
Source: Neuroscience Published:2016

Abstract

Amphetamine withdrawal (AW) is accompanied by diminished pleasure and depression which plays a key role in drug relapse and addictive behaviors. There is no efficient treatment for AW-induced depression and underpinning mechanisms were not well determined. Considering both transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and N-Methyl- d-aspartate (NMDA) receptors contribute to pathophysiology of mood and addictive disorders, in this study, we investigated the role of TRPV1 and NMDA receptors in mediating depressive-like behaviors following AW in male mice. Results revealed that administration of capsaicin, TRPV1 agonist, (100 μg/mouse, i.c.v.) and MK-801, NMDA receptor antagonist (0.005 mg/kg, i.p.) reversed AW-induced depressive-like behaviors in forced swimming test (FST) and splash test with no effect on animals' locomotion. Co-administration of sub-effective doses of MK-801 (0.001 mg/kg, i.p.) and capsaicin (10 μg/mouse, i.c.v) exerted antidepressant-like effects in behavioral tests. Capsazepine, TRPV1 antagonist, (100 μg/mouse, i.c.v) and NMDA, NMDA receptor agonist (7.5 mg/kg, i.p.) abolished the effects of capsaicin and MK-801, respectively. None of aforementioned treatments had any effect on behavior of control animals. Collectively, our findings showed that activation of TRPV1 and blockade of NMDA receptors produced antidepressant-like effects in male mice following AW, and these receptors are involved in AW-induced depressive-like behaviors. Further, we found that rapid antidepressant-like effects of capsaicin in FST and splash test are partly mediated by NMDA receptors. © 2016.