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.

Haj-Mirzaian, Arya. and Kordjazy, Nastaran. and Amiri, Shayan. and Haj-Mirzaian, Arvin. and Amini-Khoei, Hossien. and Ostadhadi, Sattar. and Dehpour, Ahmad Reza. (2016) 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. European journal of pharmacology, 780.

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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 30mg/kg) and ondansetron (0.01 and 0.1µg/kg) significantly decreased the immobility time in forced swimming test (FST) and tail-suspension test (TST). Co-administration of subeffective doses of tropisetron (1mg/kg) and ondansetron (0.001µg/kg) with subeffective dose of l-NAME (10mg/kg, nonselective NO synthase (NOS) inhibitor) and 7-nitroindazole (25mg/kg, neural NOS inhibitor) exerted antidepressant-like effect in FST and TST, while aminoguanidine (50mg/kg, inducible NOS inhibitor) did not enhance the antidepressant-like effect of 5-HT3 antagonists. Besides, l-arginine (750mg/kg, NO precursor) and sildenafil (5mg/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.

Item Type: Article
Uncontrolled Keywords: Antidepressant; Forced swimming test (FST); Nitric oxide cyclic-guanosine monophosphate (NO-cGMP); Ondansetron; Tail suspension test (TST); Tropisetron
Subjects: WM Psychiatry
QV pharmacology
Divisions: Reserach Vice-Chancellar Department > Medical Plants Research Center
Depositing User: zahra bagheri .
Date Deposited: 30 Dec 2017 07:23
Last Modified: 07 Apr 2018 04:25
URI: http://eprints.skums.ac.ir/id/eprint/6748

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