Role of 5-HT1A and 5-HT1B receptors in the antidepressant-like effect of piperine in the forced swim test

Our previous studies have showed that treating mice with piperine significantly decreased the immobility time of the animals in the forced swim test and tail suspension test, which was related to up-regulation of serotonin (5-HT) level in the brain. The purpose of this study is to explore the contribution of 5-HT receptors in the antidepressant-like effect of piperine. The results showed that pretreating mice with methiothepin (a non-selective 5-HT receptor antagonist, 0.1 mg/kg, intraperitoneally), 4-(2'-methoxy-phenyl)-1-[2'-(n-2 ''-pyridinyl)-p-iodobenzamino]ethyl-piperazine (a selective 5-HT1A receptor antagonist, 1 mg/kg, subcutaneously) or 1-(2-(1-pyrrolyl)-phenoxy)-3-isopropylamino-2-propanol (a 5-HT1B receptor antagonist, 2.5 mg/kg, intraperitoneally) was found to abolish the anti-immobility effect of piperine (10 mg/kg, intraperitoneally) in the forced swim test. On the other hand, a sub-effective dose of piperine (1 mg/kg, intraperitoneally) produced a synergistic antidepressant-like effect with (+)-8-hydroxy-2-(di-n-propylamino)tetralin (a 5-HT1A receptor agonist, 1 mg/kg, intraperitoneally) or anpirtoline (a 5-HT, B receptor agonist, 0.25 mg/kg, intraperitoneally). Taken together, these results suggest that the antidepressant-like effect of piperine in the mouse forced swim test may be mediated, at least in part, by the activation of 5-HT1A and 5-HT1B receptors. (C) 2011 Elsevier Ireland Ltd. All rights reserved.