title: Attenuation of oxidative and nitrosative stress in cortical area associates with antidepressant-like effects of tropisetron in male mice following social isolation stress.
abstract: Tropisetron, a 5-HT3 receptor antagonist widely used as an antiemetic, has been reported to have positive effects on mood disorders. Adolescence is a critical period during the development of brain, where exposure to chronic stress during this time is highly associated with the development of depression. In this study, we showed that 4 weeks of juvenile social isolation stress (SIS) provoked depressive-like behaviors in male mice, which was associated with disruption of mitochondrial function and nitric oxide overproduction in the cortical areas. In this study, tropisetron (5mg/kg) reversed the negative behavioral effects of SIS in male mice. We found that the effects of tropisetron were mediated through mitigating the negative activity of inducible nitric oxide synthase (iNOS) on mitochondrial activity. Administration of aminoguanidine (specific iNOS inhibitor, 20mg/kg) augmented the protective effects of tropisetron (1mg/kg) on SIS. Furthermore, l-arginine (nitric oxide precursor, 100mg/kg) abolished the positive effects of tropisetron. These results have increased our knowledge on the pivotal role of mitochondrial function in the pathophysiology of depression, and highlighted the role of 5-HT3 receptors in psychosocial stress response during adolescence. Finally, we observed that tropisetron alleviated the mitochondrial dysfunction through decreased nitrergic system activity in the cerebral cortex.
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box: 13145-784, 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: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran; Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Shayan
authors.initials: S
authors.lastname: Amiri
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box: 13145-784, 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: Department of Human Anatomy & Cell Science, Faculty of Medicine, University of Manitoba, Room 124, BMSB, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rahimi-Balaei
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box: 13145-784, 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: Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Carl O
authors.initials: CO
authors.lastname: Olson
authors.affiliation: Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
authors.forename: Mojgan
authors.initials: M
authors.lastname: Rastegar
authors.affiliation: Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Naserzadeh
authors.affiliation: Department of Human Anatomy & Cell Science, Faculty of Medicine, University of Manitoba, Room 124, BMSB, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada.
authors.forename: Hassan
authors.initials: H
authors.lastname: Marzban
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Zanjan Applied Pharmacology Research Center, Zanjan University of Medical sciences, Zanjan, Iran; Department of Pharmacology and Toxicology, School of Pharmacy, Zanjan University of Medical Sciences, P.O. Box: 45139-56184, Zanjan, Iran. Electronic address: jamal_hossini@yahoo.com.
authors.forename: Mir-Jamal
authors.initials: MJ
authors.lastname: Hosseini
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran.
authors.forename: Elika
authors.initials: E
authors.lastname: Samiei
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box: 13145-784, Tehran, Iran. Electronic address: ejtemam@gmail.com.
authors.forename: Shahram Ejtemaei
authors.initials: SE
authors.lastname: Mehr
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009042:Motivation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism*; D015538:Nitrosation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012934:Social Isolation / Q000523:psychology*; D013315:Stress, Psychological / Q000188:drug therapy* / Q000473:pathology; D000077526:Tropisetron
chemical_list: D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D009566:Nitrates; D017382:Reactive Oxygen Species; D000077526:Tropisetron; D019331:NG-Nitroarginine Methyl Ester
keywords: Adolescence social isolation stress; Depressive-like behaviors; Mitochondrial dysfunction; Nitric oxide; Tropisetron