| First Author | Oyola MG | Year | 2012 |
| Journal | Endocrinology | Volume | 153 |
| Issue | 2 | Pages | 837-46 |
| PubMed ID | 22186418 | Mgi Jnum | J:181716 |
| Mgi Id | MGI:5313768 | Doi | 10.1210/en.2011-1674 |
| Citation | Oyola MG, et al. (2012) Anxiolytic effects and neuroanatomical targets of estrogen receptor-beta (ERbeta) activation by a selective ERbeta agonist in female mice. Endocrinology 153(2):837-46 |
| abstractText | The dichotomous anxiogenic and anxiolytic properties of estrogens have been reported to be mediated by two distinct neural estrogen receptors (ER), ERalpha and ERbeta, respectively. Using a combination of pharmacological and genetic approaches, we confirmed that the anxiolytic actions of estradiol are mediated by ERbeta and extended and these observations to demonstrate the neuroanatomical targets involved in ERbeta activation in these behavioral responses. We examined the effects of the biologically active S-enantiomer of diarylpropionitrile (S-DPN) on anxiety-related behavioral measures, the corresponding stress hormonal response to hypothalamo-pituitary-adrenal axis reactivity, and potential sites of neuronal activation in mutant female mice carrying a null mutation for ERbeta gene (betaERKO). S-DPN administration significantly reduced anxiety-like behaviors in the open field, light-dark exploration, and the elevated plus maze (EPM) in ovariectomized wild-type (WT) mice, but not in their betaERKO littermates. Stress-induced corticosterone (CORT) and ACTH were also attenuated by S-DPN in the WT mice but not in the betaERKO mice. Using c-fos induction after elevated plus maze, as a marker of stress-induced neuronal activation, we identified the anterodorsal medial amygdala and bed nucleus of the stria terminalis as the neuronal targets of S-DPN action. Both areas showed elevated c-fos mRNA expression with S-DPN treatment in the WT but not betaERKO females. These studies provide compelling evidence for anxiolytic effects mediated by ERbeta, and its neuroanatomical targets, that send or receive projections to/from the paraventricular nucleus, providing potential indirect mode of action for the control of hypothalamo-pituitary-adrenal axis function and behaviors. |
