Department of Psychology, Santa Clara University, 500 El Camino Real, Santa Clara, CA, 95053, USA.
Department of Psychology, Santa Clara University, 500 El Camino Real, Santa Clara, CA, 95053, USA.
Behav Brain Res. 2021 May 21;406:113241. doi: 10.1016/j.bbr.2021.113241. Epub 2021 Mar 13.
Early life stress can induce lifelong emotional and social behavioral deficits that may in some cases be alleviated by drugs or alcohol. A model for early life stress, rodent maternal separation, recapitulates these behavioral sequelae, which are not limited to potentiated anxiety-like behavior, attenuated social motivation, and altered reward-seeking. Here we employed mouse maternal separation with early weaning (MSEW), consisting of pup-dam separation lasting 4-8 hours on postnatal days (PD) 2-16, with early weaning on PD 17. Prior MSEW studies have limited subjects by age or sex, so we more comprehensively investigated MSEW effects in both sexes, during adolescence and adulthood. We found universal effects of MSEW to include lifelong enhancement of anxiety-like and despair behavior, as well as deficits in social motivation. We also observed some sex-dependent effects of MSEW, namely that female MSEW mice exhibited social habituation to a greater degree than their male counterparts. Low dose ethanol administration had no major effects on the social behavior of non-stressed mice. But interestingly, MSEW-induced social habituation was counteracted by low dose ethanol in adolescent female mice, and potentiated in adolescent male mice. These effects were absent in adult animals, suggesting that ethanol may exert differential effects on the developing brain in such a manner to produce age-, sex-, and stress-dependent effects upon social behavior. Together, results indicate that MSEW reliably produces long-lasting impairments in emotional and social behaviors in both sexes and across the lifespan, but may exert more salient social behavioral effects on female animals.
早期生活压力会导致终生的情绪和社会行为缺陷，而某些情况下，药物或酒精可以缓解这些缺陷。一种早期生活压力模型，即啮齿动物母婴分离，重现了这些行为后果，这些后果不仅包括增强的焦虑样行为、社会动机减弱和奖励寻求改变。在这里，我们采用了早期断奶的幼鼠母婴分离（MSEW）模型，包括在出生后第 2-16 天对幼崽-母鼠进行 4-8 小时的分离，然后在第 17 天进行早期断奶。先前的 MSEW 研究受限于年龄或性别，因此我们更全面地在青春期和成年期的两性中研究了 MSEW 的影响。我们发现 MSEW 的普遍影响包括终生增强焦虑样和绝望行为，以及社会动机缺陷。我们还观察到 MSEW 的一些性别依赖性影响，即雌性 MSEW 小鼠表现出比雄性更大程度的社交习惯化。低剂量乙醇给药对未受压力的小鼠的社交行为没有重大影响。但有趣的是，在青春期雌性小鼠中，低剂量乙醇可以抵消 MSEW 诱导的社交习惯化，而在青春期雄性小鼠中则增强。这些影响在成年动物中不存在，这表明乙醇可能以不同的方式对发育中的大脑产生不同的影响，从而对社交行为产生年龄、性别和应激依赖性的影响。总之，结果表明 MSEW 确实会在两性和整个生命周期中产生持久的情绪和社交行为障碍，但可能对雌性动物产生更明显的社交行为影响。
