Preliminary evidence of increased alcohol use associated with ethinyl estradiol levels in women using oral contraceptives

Strzelecki, Ashley M.; Gipson, Cassandra D.; Childs, Emma; Weafer, Jessica

doi:10.1016/j.dadr.2023.100194

Cited by 2 publications

(1 citation statement)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Women exhibit an accelerated onset of, and a higher probability for developing, AUD with the same history of alcohol use as their male counterparts in a phenomenon known as the telescoping effect; further, binge-like patterns of alcohol consumption are increasingly prevalent 39,[42][43][44] . Both binge alcohol drinking and related diseases emerge in women during puberty when ovarian-derived and related hormones begin to fluctuate across the menstrual cycle, and decades of research have found positive associations between circulating concentration of ovarian E2 across the menstrual cycle and alcohol drinking behavior [45][46][47][48] . It is well-established in preclinical rodent models that females consume more alcohol than their male counterparts [49][50][51][52][53] , and ovarian hormones likely contribute to this phenomenon.…”

Section: Introductionmentioning

confidence: 99%

Rapid nongenomic estrogen signaling controls alcohol drinking behavior

Zallar,

Rivera-Irizarry,

Hamor

et al. 2023

Preprint

View full text Add to dashboard Cite

The overconsumption of alcohol contributes to a multitude of negative health outcomes, especially in women, who are more susceptible to its effects and more likely to develop alcohol dependence than men with the same early history of alcohol consumption. Binge alcohol drinking is prominent during reproductive years and correlated with high circulating estrogen in women, and rodent studies show that female rodents with intact ovaries consume more alcohol than males. However, the causal role of ovarian E2 in intact animals in alcohol drinking has not been established. Here, we show that intact female mice consume more alcohol and display reduced avoidance behavior when they have elevated levels of circulating E2 during proestrus compared to other estrous cycle stages in individual mice. We found that high ovarian E2 promotes alcohol drinking in females, but not anxiolysis, through rapid nongenomic E2 signaling at ERα in the bed nucleus of the stria terminalis (BNST). Acute administration of intra-BNST E2 in low ovarian E2 mice enhanced binge alcohol intake, while acute systemic inhibition of E2 synthesis and acute blockade of ERα signaling in the BNST reversed the pro-drinking effects of high ovarian E2 status. In contrast, acute E2 manipulations were unable to alter the effects of ovarian E2 status on avoidance behavior, suggesting genomic mechanisms are required for the anxiolytic effects of ovarian E2. We further show that corticotropin-releasing factor (CRF) neurons in the BNST are an important mediator of these effects of rapid E2 signaling, as high E2 rapidly enhanced synaptic excitation of BNSTCRFneurons and promoted their pro-alcohol drinking behavioral role. Thus, we uncover a mechanism by which ovarian hormones in intact female mice control alcohol drinking behavior, and we provide the first mechanism by which ovarian E2 control of behavior is mediated by a rapid, nongenomic signaling mechanism.

show abstract

Section: Introductionmentioning

confidence: 99%

Rapid nongenomic estrogen signaling controls alcohol drinking behavior

Zallar,

Rivera-Irizarry,

Hamor

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Rapid nongenomic estrogen signaling controls alcohol drinking behavior in mice

Zallar,

Rivera-Irizarry,

Hamor

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Ovarian-derived estrogen can signal non-canonically at membrane-associated receptors in the brain to rapidly regulate neuronal function. Early alcohol drinking confers greater risk for alcohol use disorder in women than men, and binge alcohol drinking is correlated with high estrogen levels, but a causal role for estrogen in driving alcohol drinking has not been established. We found that female mice displayed greater binge alcohol drinking and reduced avoidance when estrogen was high during the estrous cycle than when it was low. The pro-drinking, but not anxiolytic, effect of high endogenous estrogen occurred via rapid 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. Thus, this study demonstrates a rapid, nongenomic signaling mechanism for ovarian-derived estrogen in the brain controlling behavior in gonadally intact females.

show abstract

Preliminary evidence of increased alcohol use associated with ethinyl estradiol levels in women using oral contraceptives

Cited by 2 publications

References 31 publications

Rapid nongenomic estrogen signaling controls alcohol drinking behavior

Rapid nongenomic estrogen signaling controls alcohol drinking behavior

Rapid nongenomic estrogen signaling controls alcohol drinking behavior in mice

Contact Info

Product

Resources

About