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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 Publisher Pubmed



Hajmirzaian A1, 2 ; Amiri S1, 2 ; Kordjazy N1, 2 ; Momeny M1, 2 ; Razmi A3 ; Rahimibalaei M4 ; Aminikhoei H1, 2 ; Marzban H5 ; Mehr SE1, 2 ; Dehpour AR1, 2 ; Ghaffari SH6
Authors
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Authors Affiliations
  1. 1. Experimental Medicine Research Center, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran
  2. 2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran
  3. 3. Institute of Medicinal Plants, Academic Center for Education, Culture and Research (ACECR), Supa Boulevard, P.O. Box 31375-1369, Pouleh Kordan, Karaj, Iran
  4. 4. Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, BMSB, 745 Bannatyne Avenue, Winnipeg, R3E 0J9, MB, Canada
  5. 5. Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, Winnipeg, R3E 0J9, MB, Canada
  6. 6. Hematology, Oncology and Stem Cell Transplantation Research Center, University of Tehran Medical Sciences, Shariaty Hospital, Tehran, Iran

Source: Neuroscience Published:2016


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. © 2015 IBRO.
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