Involvement of Nitric Oxide-Cyclic Guanosine Monophosphate Pathway in the Antidepressant-Like Effect of Tropisetron and Ondansetron in Mice Forced Swimming Test and Tail Suspension Test Publisher Pubmed



Hajmirzaian A^{1, 2} ; Kordjazy N^{1, 2} ; Amiri S^{1, 2} ; Hajmirzaian A^{1, 2} ; Aminikhoei H^{1, 2} ; Ostadhadi S^{1, 2, 3} ; Dehpour A^{1, 2}
Source: European Journal of Pharmacology Published:2016

Abstract

Antidepressant-like effects of 5-hydroxytryptamine subtype 3 (5-HT3) antagonists including tropisetron and ondansetron have been previously demonstrated in the literature. It was reported that stimulation of 5-HT3 receptors activate the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, which is involved in regulation of behavioral and emotional functions. In our study, treating animals with tropisetron (5, 10, and 30 mg/kg) and ondansetron (0.01 and 0.1 μg/kg) significantly decreased the immobility time in forced swimming test (FST) and tail-suspension test (TST). Co-administration of subeffective doses of tropisetron (1 mg/kg) and ondansetron (0.001 μg/kg) with subeffective dose of l-NAME (10 mg/kg, nonselective NO synthase (NOS) inhibitor) and 7-nitroindazole (25 mg/kg, neural NOS inhibitor) exerted antidepressant-like effect in FST and TST, while aminoguanidine (50 mg/kg, inducible NOS inhibitor) did not enhance the antidepressant-like effect of 5-HT3 antagonists. Besides, l-arginine (750 mg/kg, NO precursor) and sildenafil (5 mg/kg, phosphodiesterase inhibitor) suppressed the anti-immobility effect of 5-HT3 antagonists. None of the treatments altered the locomotor behavior of mice in open-field test. Also, hippocampal (but not cortical) nitrite level was significantly lower in tropisetron and ondansetron-treated mice compared with saline-injected mice. Also, co-administration of 7-nitroindazole with tropisetron or ondansetron caused a significant decrease in hippocampal nitrite levels. In conclusion, we suggest that antidepressant-like effect of tropisetron and ondansetron are partially mediated by modulation of NO-cGMP pathway. © 2016 Published by Elsevier B.V.