Rapid nongenomic estrogen signaling controls alcohol drinking behavior.

Autor:	Zallar LJ; Pharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA., Rivera-Irizarry JK; Neuroscience Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA., Hamor PU; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Pigulevskiy I; Pharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA., Rico Rozo AS; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Mehanna H; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Liu D; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Welday JP; Neuroscience Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA., Bender R; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Asfouri JJ; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Levine OB; Neuroscience Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA., Skelly MJ; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Hadley CK; Weill Cornell/Rockefeller/Sloan Kettering Tri-institutional MD-PhD Program, New York, NY 10065, USA., Fecteau KM; Endocrine Technologies Core, Oregon National Primate Research Center, Beaverton, OR, USA., Nelson S; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Miller J; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Ghazal P; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Bellotti P; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Singh A; Neuroscience Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA., Hollmer LV; Pharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA., Erikson DW; Endocrine Technologies Core, Oregon National Primate Research Center, Beaverton, OR, USA., Geri J; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA., Pleil KE; Pharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Neuroscience Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell University, New York, NY, USA.; Department of Pharmacology, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Aug 15. Date of Electronic Publication: 2024 Aug 15.
DOI:	10.1101/2023.11.02.565358
Abstrakt:	Ovarian-derived estrogen is a key modulator of numerous physiological processes via genomic and nongenomic mechanisms, including signaling non-canonically at membrane-associated estrogen receptors in the brain to rapidly regulate neuronal function. However, the mechanisms mediating estrogen regulation of behaviors such as alcohol consumption remain unclear. Early alcohol drinking confers greater risk for alcohol use disorder in women than men, and binge alcohol drinking is correlated with high circulating estrogen levels, but a causal role for estrogen signaling in driving alcohol drinking in gonadally-intact animals has not been established. We found that female mice displayed greater binge alcohol drinking and reduced avoidance behavior when circulating estrogen was high during the proestrus phase of the estrous cycle than when it was low, contributing to sex differences in these behaviors. The pro-drinking, but not anxiolytic, effect of high endogenous estrogen state occurred via rapid estrogen signaling at membrane-associated estrogen receptor alpha in the bed nucleus of the stria terminalis, which promoted synaptic excitation of corticotropin-releasing factor neurons and facilitated their activity during alcohol drinking behavior. This study is the first to demonstrate a rapid, nongenomic signaling mechanism for ovarian-derived estrogen signaling in the brain controlling behavior in gonadally intact females, and it establishes a causal role for estrogen in an intact hormonal context for driving alcohol consumption that contributes to known sex differences in this behavior. Competing Interests: Competing interests Authors declare that they have no competing interests.
Databáze:	MEDLINE
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