Steinman Michael Q, Trainor Brian C
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, U.S.A.
Department of Psychology and Center for Neuroscience, University of California, Davis, CA 95616, U.S.A..
Semin Cell Dev Biol. 2017 Jan;61:92-98. doi: 10.1016/j.semcdb.2016.06.021. Epub 2016 Jun 30.
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.
被诊断患有重度抑郁症的女性人数几乎是男性的两倍，但在研究抑郁症生物学基础时，使用雌性动物模型的情况却落后于雄性。社会挫败模型利用社会压力来产生类似抑郁症的症状，以便研究神经生物学机制。一般来说，社会挫败很难应用于雌性啮齿动物。然而，雄性和雌性加州小鼠（加州林鼠）都具有领地意识。这使得可以在两性中研究挫败。遭受挫败的雄性往往会表现出主动应对机制，并表现出攻击性和认知灵活性降低。遭受挫败的雌性更多地采用反应性应对机制，表现为社交回避和低攻击性。重要的是，挫败对雌性社交互动行为的影响独立于成年性腺类固醇。这些行为表型与精氨酸加压素（AVP）和催产素（OT）的性别特异性变化有关，这两种密切相关的肽调节社会行为和应激反应性。在与应激反应和社会行为相关的脑区，挫败分别导致雄性AVP活性长期降低，雌性OT活性增加。鼻内给予OT被证明可模拟挫败诱导的内源性OT活性增加的效果，导致未受挫败的雌性出现社交退缩。这表明抑制OT活性可能会降低压力对雌性行为的影响。这些结果凸显了在寻找治疗情绪障碍的性别特异性药理学方法时，维持多种啮齿动物模型的价值。
