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Attenuation of glutamatergic and nitrergic system contributes to the antidepressant-like effect induced by capsazepine in the forced swimming test

Sartim, Ariandra G.a,*; Brito, Bianca M.a,*; Gobira, Pedro H.a; Joca, Sâmia R.L.a,b

doi: 10.1097/FBP.0000000000000416

The transient receptor potential vanilloid 1 (TRPV1) can modulate stress-related behaviours, thus representing an interesting target for new antidepressant drugs. TRPV1 can trigger glutamate release and nitric oxide synthesis in the brain, mechanisms also involved in the neurobiology of depression. However, it is not known if these mechanisms are involved in TRPV1-induced behavioural effects. Therefore, the aim of this study was to verify if the antidepressant-like effect induced by a TRPV1 antagonist in mice submitted to the forced swimming test (FST) would be facilitated by combined treatment with neuronal nitric oxide synthase (nNOS) inhibition and N-methyl-D-aspartate (NMDA) blockade. Male Swiss mice were given (intracerebroventricular) injections of capsazepine (CPZ) (TRPV1 antagonist – 0.05/0.1/0.3/0.6 nmol/µl), and AP7 (NMDA antagonist – 1/3/10 nmol/µl) or N-propyl-L-arginine (NPA, nNOS inhibitor – 0.001/0.01/0.1 nmol/µl), and 10 min later, submitted to an open field test, and immediately afterwards, to the FST. An additional group received coadministration of CPZ and AP7 or CPZ and NPA, in subeffective doses. The results demonstrated that CPZ (0.1 nmol/µl), AP7 (3 nmol/µl) and NPA (0.01/0.1 nmol/µl) induced antidepressant-like effects. Moreover, coadministration of subeffective doses of CPZ and AP7 or CPZ and NPA induced significant antidepressant-like effects. Altogether, the data indicate that blockade of TRPV1 receptors by CPZ induces antidepressant-like effects and that both nNOS inhibition and NMDA blockade facilitate CPZ effects in the FST.

aDepartment of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil

bTranslational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

* Ariandra G. Sartim and Bianca M. Brito contributed equally to the writing of this article.

Correspondence to Sâmia R.L. Joca, Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP), University of São Paulo (USP), Café Av, s/n, Ribeirão Preto, São Paulo 14040-903, Brazil E-mail:

Received March 12, 2018

Accepted May 23, 2018

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