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      Sex differences in the effects of social defeat on brain and behavior in the California mouse: insights from a monogamous rodent

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          Abstract

          Women are nearly twice as likely as men to be diagnosed with major depressive disorder, yet the use of female animal models in studying the biological basis of depression lags behind that of males. The social defeat model uses social stress to generate depression-like symptoms in order to study the neurobiological mechanisms. In general, social defeat is difficult to apply in female rodents. However, male and female California mice ( Peromyscus californicus) are territorial. This allows defeat to be studied in both sexes. Males exposed to defeat tend to exhibit proactive coping mechanisms and demonstrate aggression and reduced cognitive flexibility. Females exposed to defeat engage more in reactive coping mechanisms which is highlighted by social avoidance and low aggression. Importantly, effects of defeat on social interaction behavior in females is independent of adult gonadal steroids. These behavioral phenotypes are associated with sex-specific changes in arginine vasopressin (AVP) and oxytocin (OT), closely related peptides that regulate social behavior and stress reactivity. In brain regions associated with stress responses and social behavior, defeat induced long term decreases in AVP activity and increases in OT activity in males and females respectively. Intranasal OT administration was shown to mimic the effects of defeat-induced increases in endogenous OT activity, causing social withdrawal in undefeated females. This suggests that inhibition of OT activity could reduce the impact of stress on behavior in females. These results highlight the value of maintaining diverse rodent models in the search for sex-specific pharmacological approaches to treating mood disorders.

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          Author and article information

          Journal
          9607332
          20707
          Semin Cell Dev Biol
          Semin. Cell Dev. Biol.
          Seminars in cell & developmental biology
          1084-9521
          1096-3634
          19 July 2016
          30 June 2016
          January 2017
          01 January 2018
          : 61
          : 92-98
          Affiliations
          [a ]Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037
          [b ]Department of Psychology and Center for Neuroscience, University of California, Davis, CA 95616
          Author notes
          Correspondence: Brian C. Trainor, Department of Psychology, University of California Davis, CA 95616 bctrainor@ 123456ucdavis.edu
          Article
          PMC5201444 PMC5201444 5201444 nihpa803553
          10.1016/j.semcdb.2016.06.021
          5201444
          27375045
          980c5db3-e1da-42f1-b873-c266ff590806
          History
          Categories
          Article

          Social defeat,Aggression,Nonapeptides, Peromyscus ,Sex differences,Social behavior

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