title: Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1β and nitric oxide on hypothalamic-pituitary-adrenal axis function.
abstract: The neuroimmune-endocrine dysfunction has been accepted as one of fundamental mechanisms contributing to the pathophysiology of psychiatric disorders including depression and anxiety. In this study, we aimed to evaluate the involvement of hypothalamic-pituitary-adrenal (HPA) axis, interleukin-1β, and nitrergic system in mediating the negative behavioral impacts of juvenile social isolation stress (SIS) in male mice. We also investigated the possible protective effects of lithium on behavioral and neurochemical changes in socially isolated animals. Results showed that experiencing 4-weeks of juvenile SIS provoked depressive and anxiety-like behaviors that were associated with hyper responsiveness of HPA axis, upregulation of interleukin-1β, and nitric oxide (NO) overproduction in the pre-frontal cortex and hippocampus. Administration of lithium (10 mg/kg) significantly attenuated the depressant and anxiogenic effects of SIS in behavioral tests. Lithium also restored the negative effects of SIS on cortical and hippocampal interleukin-1β and NO as well as HPA axis deregulation. Unlike the neutralizing effects of l-arginine (NO precursor), administration of l-NAME (3 mg/kg) and aminoguanidine (20 mg/kg) potentiated the positive effects of lithium on the behavioral and neurochemical profile of isolated mice. In conclusion, our results revealed that juvenile SIS-induced behavioral deficits are associated with abnormalities in HPA-immune function. Also, we suggest that alleviating effects of lithium on behavioral profile of isolated mice may be partly mediated by mitigating the negative impact of NO on HPA-immune function.
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: arya.mirzaian@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Haj-Mirzaian
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: from.here.till.there@gmail.com.
authors.forename: S
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. Electronic address: nastaran.kordjazy@gmail.com.
authors.forename: N
authors.initials: N
authors.lastname: Kordjazy
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: m.momeni@yahoo.com.
authors.forename: M
authors.initials: M
authors.lastname: Momeny
authors.affiliation: Institute of Medicinal Plants, Academic Center for Education, Culture and Research (ACECR), Supa Boulevard, Pouleh Kordan, P.O. Box 31375-1369, Karaj, Iran. Electronic address: a.razmi@yahoo.com.
authors.forename: A
authors.initials: A
authors.lastname: Razmi
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. Electronic address: maryam_rahimib@yahoo.com.
authors.forename: M
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. Electronic address: aminikhoyi@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Amini-Khoei
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: arvin.mirzaian@gmail.com.
authors.forename: A
authors.initials: A
authors.lastname: Haj-Mirzaian
authors.affiliation: Department of Human Anatomy & Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada. Electronic address: Hassan.Marzban@my.umanitoba.ca.
authors.forename: H
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. Electronic address: ejtemam@gmail.com.
authors.forename: S E
authors.initials: SE
authors.lastname: Mehr
authors.affiliation: Hematology, Oncology & Stem Cell Transplantation Research Center, University of Tehran Medical Sciences, Shariaty Hospital, Tehran, Iran. Electronic address: shghaffari@tums.ac.ir.
authors.forename: S H
authors.initials: SH
authors.lastname: Ghaffari
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: dehpour@yahoo.com.
authors.forename: A R
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D018020:Lithium Compounds / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D012934:Social Isolation; D013315:Stress, Psychological / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D018020:Lithium Compounds; D009573:Nitrites; D009569:Nitric Oxide; D003345:Corticosterone
keywords: depressive-like behaviors; hypothalamic–pituitary–adrenal axis; interlukine-1β; juvenile social isolation stress; lithium; nitric oxide