title: Blockade of NMDA receptors reverses the depressant, but not anxiogenic effect of adolescence social isolation in mice.
abstract: Early life social isolation stress (SIS), a well-known chronic stress paradigm, is contributed to a number of pathophysiological and neurochemical changes including depression and anxiety. The underlying mechanisms for these disorders in socially isolated animals have not been fully cleared. Previous studies have shown that N-Methyl-d-aspartate (NMDA) receptor function is changed by social isolation condition. It is now well recognized that NMDA receptor blockade can exhibit antidepressant and anxiolytic actions. In our study, postnatal day 21-25 mice were randomly housed for 4 weeks under either social condition (SC) or isolated condition (IC). Then, animals were subjected to different behavioral experiments to investigate whether blockade of NMDA receptor resulted in behavioral alterations in animals. Social isolation stress induced depressive and anxiety-like behaviors in IC animals in comparison with SC mice. Also, we applied subeffective doses of antagonists including ketamine (1mg/kg), MK-801 (0.05mg/kg), and magnesium sulfate (10mg/kg) to both SC and IC mice prior to behavioral experiments. Administration of a single dose of all mentioned drugs did not affect the SC mice but modulated the depressant effects of SIS on IC mice. Administration of NMDA receptor antagonists decreased the immobility time in the forced swimming test as well as an increase in grooming behavior in splash test. However, anxiety-like behaviors in IC animals remained unchanged in hole-board test and open field test after blockade of NMDA receptors. Taken together, our results showed the possible involvement of the NMDA receptors in the depressive, but not anxiety-like behaviors induced by SIS.
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, 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, 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, Tehran, Iran.
authors.forename: Nastaran
authors.initials: N
authors.lastname: Kordjazy
authors.affiliation: Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Maryam
authors.initials: M
authors.lastname: Rahimi-Balaei
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Arvin
authors.initials: A
authors.lastname: Haj-Mirzaian
authors.affiliation: Department of Human Anatomy and Cell Science, College of Medicine, Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Hassan
authors.initials: H
authors.lastname: Marzban
authors.affiliation: Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Aminzadeh
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: ejtemam@gmail.com.
authors.forename: Shahram Ejtemaei
authors.initials: SE
authors.lastname: Mehr
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000523:psychology*; D008297:Male; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012934:Social Isolation / Q000523:psychology*; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D016194:Receptors, N-Methyl-D-Aspartate
keywords: Anxiety; Depressive-like behaviors; Mice; N-Methyl-d-aspartate receptor; Social isolation stress