Department of Psychology, University of Wisconsin-Madison, United States.
Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, United States.
Brain Res. 2019 May 1;1710:102-108. doi: 10.1016/j.brainres.2018.12.040. Epub 2018 Dec 27.
Early life stress (ELS) strongly impacts mental health, but little is known about its interaction with biological sex and postnatal development to influence risk and resilience to psychopathologies. A number of psychiatric disorders, such as social anhedonia and drug addiction, involve dysfunctional opioid signaling; moreover, there is evidence for differential central opioid function in males vs. females. The present study examined opioid receptor gene expression in the nucleus accumbens (NAc) and amygdala of male and female rats subjected to a neonatal predator odor exposure (POE) paradigm to model ELS. Brain tissue was collected at two developmental time points: neonatal and juvenile. Results showed that, following the neonatal POE experience, opioid receptor mRNA levels in the NAc were differentially regulated at the neonatal and juvenile time points. POE downregulated neonatal mu- and kappa-opioid receptor mRNA levels in neonatal females, but upregulated mu- and delta-opioid receptor mRNA levels in juvenile females. Intriguingly, POE had no significant effect on NAc opioid receptor mRNA levels in males at either time point, indicating that the impact of POE on opioid system development is sex-dependent. Finally, POE failed to alter amygdalar opioid receptor gene expression in either sex at either time-point. The spatiotemporally- and sex-specific impact of ELS within the developing brain may confer differential risk or resilience for males and females to develop atypical opioid-regulated behaviors associated with conditions such as depression and addiction.
早期生活应激（ELS）强烈影响心理健康，但人们对其与生物性别和产后发育的相互作用知之甚少，这种相互作用会影响精神病理学的风险和恢复能力。许多精神疾病，如社交快感缺失和药物成瘾，涉及到阿片样物质信号传递功能障碍；此外，有证据表明，雄性和雌性动物的中枢阿片功能存在差异。本研究通过对新生期捕食者气味暴露（POE）模型进行检测，以研究ELS 对雄性和雌性大鼠伏隔核（NAc）和杏仁核阿片受体基因表达的影响。在两个发育时间点收集脑组织：新生儿和青少年。结果表明，在经历新生 POE 后，NAc 中的阿片受体 mRNA 水平在新生儿和青少年时期呈现不同的调节。POE 下调了新生雌性大鼠 NAc 中 mu- 和 kappa-阿片受体 mRNA 水平，但上调了幼年雌性大鼠的 mu- 和 delta-阿片受体 mRNA 水平。有趣的是，POE 对雄性大鼠在任何时间点的 NAc 阿片受体 mRNA 水平均无显著影响，表明 POE 对阿片系统发育的影响具有性别依赖性。最后，POE 未能改变两性在任何时间点的杏仁核阿片受体基因表达。在发育中的大脑中，ELS 的时空和性别特异性影响可能会使男性和女性在发展与抑郁和成瘾等情况相关的非典型阿片调节行为方面具有不同的风险或恢复能力。
