The role of rapid estrogen signaling in alcohol drinking behavior

Project Summary/Abstract Binge alcohol drinking is a major risk factor for many diseases, including alcohol use disorder (AUD) and other neuropsychiatric diseases, and women are at greater risk for developing AUD than men with the same history of alcohol use. The sex hormone estrogen, which fluctuates across the menstrual/estrous cycle in females, has been implicated in playing a regulatory role in alcohol drinking behavior across mammalian species, but the specific mechanisms underlying this function are not well understood. We recently found that ovarian estrogen acts via rapid, nongenomic signaling at membrane-associated estrogen receptors in the limbic system to drive binge alcohol drinking behavior in gonadally intact female mice. We hypothesize that estrogen regulates presynaptic neurotransmitter release and postsynaptic excitability in a coordinated fashion to regulate the activation and signaling of critical neuropeptidergic circuits that promote alcohol use. In the proposed work, we examine the circuit and receptor signaling context for rapid E2 modulation of neuronal function that drives binge alcohol drinking in intact female mice. These studies will improve our understanding of this behavior in females, potentially providing new avenues for pharmacotherapeutic approaches to curbing excessive alcohol consumption.