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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 A1, 2 ; Kordjazy N1, 2 ; Amiri S1, 2 ; Hajmirzaian A1, 2 ; Aminikhoei H1, 2 ; Ostadhadi S1, 2, 3 ; Dehpour A1, 2
Authors
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Authors Affiliations
  1. 1. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran
  3. 3. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

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.
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