Estrogen receptor 尾 and oxytocin interact to modulate anxiety-like behavior and neuroendocrine stress reactivity in adult male and female rats

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• 作者：Andrea E. Kudwa^a ; ¹ ; Robert F. McGivern^b ; Robert J. Handa^a ; ^c ; ^{rhanda@arizona.edu" class="auth_mail}
• 关键词：3尾-diol ; 5 alpha androstane 3尾 ; 17尾 diol ; ACTH ; adrenocorticotrophic hormone ; CORT ; corticosterone ; CRH ; corticotropin releasing hormone ; DRN ; dorsal raphe nucleus ; E2 ; estradiol ; HPA ; hypothalamo-pituitary-adrenal ; PVN ; paraventricular nucleus ; T ; testosterone ; TPH2 ; tryptophan hydroxylase 2 ; ER尾 ; estrogen receptor beta ; ER伪 ; estrogen receptor alpha ; OT ; oxytocin ; EPM ; elevated plus maze ; VEH ; vehicle ; AR ; androgen receptor ; GABA ; gamma amino butyric acid ; ER尾KO ; estrogen receptor beta kno
• 刊名：Physiology and Behavior
• 出版年：22 April, 2014
• 年：2014
• 卷：129
• 期：Complete
• 页码：287-296
• 全文大小：806 K

文摘

The hypothalamic-pituitary-adrenal (HPA) axis is activated in response to stressors and is controlled by neurons residing in the paraventricular nucleus of the hypothalamus (PVN). Although gonadal steroid hormones can influence HPA reactivity to stressors, the exact mechanism of action is not fully understood. It is known, however, that estrogen receptor 尾 (ER尾) inhibits HPA reactivity and decreases anxiety-like behavior in rodents. Since ER尾 is co-expressed with oxytocin (OT) in neurons of the PVN, an ER尾-selective agonist was utilized to test the whether ER尾 decreases stress-induced HPA reactivity and anxiety-like behaviors via an OTergic pathway. Adult gonadectomized male and female rats were administered diarylpropionitrile, or vehicle, peripherally for 5 days. When tested for anxiety-like behavior on the elevated plus maze (EPM), diarylpropionitrile-treated males and females significantly increased time on the open arm of the EPM compared to vehicle controls indicating that ER尾 reduces anxiety-like behaviors. One week after behavioral evaluation, rats were subjected to a 20 minute restraint stress. Treatment with diarylpropionitrile reduced CORT and ACTH responses in both males and females. Subsequently, another group of animals was implanted with cannulae directed at the lateral ventricle. One week later, rats underwent the same protocol as above but with the additional treatment of intracerebroventricular infusion with an OT antagonist (des Gly-NH₂ d(CH₂)₅ [Tyr(Me)², Thr⁴] OVT) or VEH, 20 min prior to behavioral evaluation. OT antagonist treatment blocked the effects of diarylpropionitrile on the display of anxiety-like behaviors and plasma CORT levels. These data indicate that ER尾 and OT interact to modulate the HPA reactivity and the display of anxiety-like behaviors.