A possible participation of transient receptor potential vanilloid type 1 channels in the antidepressant effect of fluoxetine

Shyamshree S.S. Manna, Sudhir N. Umathe

Index: Eur. J. Pharmacol. 685(1-3) , 81-90, (2012)

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Abstract

The present study investigated the influence of transient receptor vanilloid type 1 (TRPV1) channel agonist (capsaicin) and antagonist (capsazepine) either alone or in combination with traditional antidepressant drug, fluoxetine; or a serotonin hydroxylase inhibitor, para-chlorophenylalanine; or a glutamate N-methyl-d-aspartate (NMDA) receptor agonist, NMDA on the forced swim test and tail suspension test using male Swiss mice. Results revealed that intracerebroventricular injections of capsaicin (200 and 300μg/mouse) and capsazepine (100 and 200μg/mouse) reduced the immobility time, exhibiting antidepressant-like activity that was comparable to the effects of fluoxetine (2.5–10μg/mouse) in both the tests. However, in the presence of inactive dose (10μg/mouse) of capsazepine, capsaicin (300μg/mouse) had no influence on the indices of both tests, signifying that the effects are TRPV1-mediated. Further, the antidepressant-like effects of both the TRPV1 ligands were neutralized in mice-pretreated with NMDA (0.1μg/mouse), suggestive of the fact that decreased glutamatergic transmission might contribute to the antidepressant-like activity. In addition, co-administration of sub-threshold dose of capsazepine (10μg/mouse) and fluoxetine (1.75μg/mouse) produced a synergistic effect in both the tests. In contrast, inactive doses of capsaicin (10 and 100μg/mouse) partially abolished the antidepressant effect of fluoxetine (10μg/mouse), while its effect was potentiated by active dose of capsaicin (200μg/mouse). Moreover, pretreatment of mice with para-chlorophenylalanine (300mg/kg/day×3days, i.p.) attenuated the effects of capsaicin and capsazepine, demonstrating a probable interplay between serotonin and TRPV1, at least in parts. Thus, our data indicate a possible role of TRPV1 in depressive-like symptoms.