Tickerhoof Maria C, Morales Lina K Nerio, Goff Jeff, Vitale Erika M, Smith Adam S
Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045.
bioRxiv. 2024 Nov 12:2024.11.11.623026. doi: 10.1101/2024.11.11.623026.
The neurobiological mechanisms underlying the connection between anxiety brought on by social stressors and the negative impact on relationship formation have remained elusive. In order to address this question, we used the social defeat model in the socially monogamous prairie vole to investigate the impact of this stress on pair bond formation. Social defeat experience inhibited partner preference formation in males but promoted preference in females. Furthermore, pair bonding increased corticotropin-releasing hormone (CRH) expression in the bed nucleus of the stria terminalis (BNST) in male prairie voles, while defeat experience increased BNST CRH expression in females. Chemogenetic excitation of BNST CRH neurons during a short cohabitation with a new partner promoted a partner preference in stress-naïve prairie voles. Interestingly, chemogenetic inhibition of BNST CRH neurons during cohabitation with a new partner blocked partner preference in stress-naïve males but promoted preference in defeated males. Inhibition of BNST CRH neurons also blocked partner preference in stress-naïve females but did not alter preference behavior in defeated females. This study revealed sexual dimorphism in not only the impact of social defeat on pair bond formation, but also in the role BNST CRHergic neurons play in regulating changes in pair bonding following social conflict.
社会应激源引发的焦虑与对关系形成的负面影响之间联系的神经生物学机制一直难以捉摸。为了解决这个问题,我们在实行社会一夫一妻制的草原田鼠中使用社会挫败模型来研究这种应激对配偶关系形成的影响。社会挫败经历抑制了雄性田鼠的伴侣偏好形成,但促进了雌性田鼠的偏好。此外,配偶关系增加了雄性草原田鼠终纹床核(BNST)中促肾上腺皮质激素释放激素(CRH)的表达,而挫败经历增加了雌性田鼠BNST中CRH的表达。在与新伴侣短暂同居期间,对BNST中CRH神经元进行化学遗传学兴奋,促进了未经历应激的草原田鼠的伴侣偏好。有趣的是,在与新伴侣同居期间,对BNST中CRH神经元进行化学遗传学抑制,阻断了未经历应激的雄性田鼠的伴侣偏好,但促进了经历过挫败的雄性田鼠的偏好。抑制BNST中CRH神经元也阻断了未经历应激的雌性田鼠的伴侣偏好,但没有改变经历过挫败的雌性田鼠的偏好行为。这项研究不仅揭示了社会挫败对配偶关系形成影响中的性别差异,还揭示了BNST中CRH能神经元在调节社会冲突后配偶关系变化中所起的作用。