摘要

Previous studies have demonstrated that prior reproductive experience can influence anxiety-like behaviors, although neural mechanisms underlying this shift remain unknown. Studies in virgin females suggest that activation of the two estrogen receptor subtypes, ER alpha and ER beta, have differing effects on anxiety. Specifically, ER beta activation has been shown to reduce anxiety-like behaviors, while ER alpha activation has no significant effect. The purpose of the present study was to examine the possible roles of ER alpha and ER beta subtypes in parity-induced alterations in anxiety-like behavior, as tested on the elevated plus maze (EPM). Groups of ovariectomized, age-matched, nulliparous and primiparous females were tested on the EPM following administration of the ER alpha agonist 4,4',4 ''-(4-Propyl-{1H}-pyrazole-1,3,5-tryl)trisphenol (PPT; 1 mg/kg), the ER beta agonist Diarylpropionitrile (DPN; 1 mg/kg) or vehicle (DMSO). All drugs were administered once daily for 4 days prior to testing as this dosing paradigm has previously been used to demonstrate anxiolytic effects of DPN in virgin rats. In addition, as exposure to the EPM is a psychological stressor, physiological markers of the stress response were measured in both plasma (corticosterone) and brain (corticotropin releasing hormone; CRH) post-EPM testing. Unexpectedly, the ER alpha agonist PPT selectively increased the time spent exploring the open arms of the EPM in non-lactating, primiparous females, with no significant effects of DPN observed in either nulliparous or primiparous subjects. All females administered PPT and tested on the EPM demonstrated significantly reduced corticosterone secretion when compared to vehicle-treated controls. In addition, significant effects of both reproductive experience and PPT administration on CRH mRNA expression were observed in both the paraventricular nucleus and amygdala using qPCR. These findings indicate that reproductive experience modulates the effects of ER alpha activation on both EPM behavior related to anxiety and CRH gene expression.

  • 出版日期2012-1