title: Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test.
abstract: Recent evidence indicates that 5-hydroxytryptamine 3 (5-HT3) antagonists such as ondansetron and tropisetron exert positive behavioral effects in animal models of depression. Due to the ionotropic nature of 5-HT3 and N-methyl-d-aspartate (NMDA) receptors, plus their contribution to the pathophysiology of depression, we investigated the possible role of NMDA receptors in the antidepressant-like effect of 5-HT3 receptor antagonists in male mice. In order to evaluate the animals' behavior in response to different treatments, we performed open-field test (OFT), forced swimming test (FST), and tail-suspension test (TST), which are considered as valid tasks for measuring locomotor activity and depressive-like behaviors in mice. Our data revealed that intraperitoneal (i.p.) administration of tropisetron (5, 10, and 30mg/kg) and ondansetron (0.01, and 0.1μg/kg) significantly decreased the immobility time in FST and TST. Also, co-administration of subeffective doses of tropisetron (1mg/kg, i.p.) or ondansetron (0.001μg/kg, i.p.) with subeffective doses of NMDA receptor antagonists, ketamine (1mg/kg, i.p.), MK-801 (0.05mg/kg, i.p.) and magnesium sulfate (10mg/kg, i.p.) resulted in a reduced immobility time both in FST and TST. The subeffective dose of NMDA (NMDA receptor agonist, 75mg/kg, i.p.) abolished the effects of 5-HT3 antagonists in FST and TST, further supporting the presumed interaction between 5-HT3 and NMDA receptors. These treatments did not affect the locomotor behavior of animals in OFT. Finally, the results of our study suggest that the positive effects of 5-HT3 antagonists on the coping behavior of mice in FST and TST are at least partly mediated through NMDA receptors participation.
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Kordjazy
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Arya
authors.initials: A
authors.lastname: Haj-Mirzaian
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Shayan
authors.initials: S
authors.lastname: Amiri
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Sattar
authors.initials: S
authors.lastname: Ostadhadi
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Amini-Khoei
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. Electronic address: dehpoura@sina.tums.ac.ir.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology*; D013550:Swimming
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D058831:Serotonin 5-HT3 Receptor Antagonists; D012701:Serotonin
keywords: 5-HT3 antagonist; Antidepressant; Forced swimming test (FST); Mice; NMDA receptor; Tail suspension test (TST)