Anxiolytic effects and neuroanatomical targets of estrogen receptor-β (ERβ) activation by a selective ERβ agonist in female mice.
Enviado por Mario G Oyola el
Título | Anxiolytic effects and neuroanatomical targets of estrogen receptor-β (ERβ) activation by a selective ERβ agonist in female mice. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Autores | Oyola, MG, Portillo, W, Reyna, A, Foradori, CD, Kudwa, A, Hinds, L, Handa, RJ, Mani, SK |
Journal | Endocrinology |
Volume | 153 |
Issue | 2 |
Pagination | 837-46 |
Date Published | 2012 Feb |
ISSN | 1945-7170 |
Palabras clave | 2-Hydroxypropyl-beta-cyclodextrin, Animals, Anti-Anxiety Agents, Anxiety, Behavior, Animal, beta-Cyclodextrins, Estrogen Receptor beta, Female, Gene Expression Regulation, Mice, Mice, Knockout, Mutation, Nitriles, Ovariectomy, Propionates, Stress, Physiological |
Abstract | The dichotomous anxiogenic and anxiolytic properties of estrogens have been reported to be mediated by two distinct neural estrogen receptors (ER), ERα and ERβ, respectively. Using a combination of pharmacological and genetic approaches, we confirmed that the anxiolytic actions of estradiol are mediated by ERβ and extended and these observations to demonstrate the neuroanatomical targets involved in ERβ 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 ERβ gene (βERKO). 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 βERKO littermates. Stress-induced corticosterone (CORT) and ACTH were also attenuated by S-DPN in the WT mice but not in the βERKO 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 βERKO females. These studies provide compelling evidence for anxiolytic effects mediated by ERβ, 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. |
DOI | 10.1210/en.2011-1674 |
Alternate Journal | Endocrinology |
PubMed ID | 22186418 |
PubMed Central ID | PMC3275390 |
Grant List | R01 NS039951 / NS / NINDS NIH HHS / United States R25 GM069234 / GM / NIGMS NIH HHS / United States NS039951-11 / NS / NINDS NIH HHS / United States |