A Weill Cornell Medicine study finds that estrogen levels drive binge drinking behavior in females. This discovery could lead to new, targeted treatments for alcohol use disorder.
A groundbreaking preclinical study by researchers at Weill Cornell Medicine has revealed that the hormone estrogen plays a significant role in regulating binge drinking behavior in females. Published today in the journal Nature Communications, the study offers compelling insights that may lead to innovative treatments for alcohol use disorder.
The research shows that elevated levels of circulating estrogen drive females to consume large quantities of alcohol, especially during the initial 30 minutes after it is made available — a behavior commonly known as “pregaming.”
“We know a lot less about what drives alcohol drinking behavior in females because most studies of alcohol use have been done in males,” Kristen Pleil, the study’s senior author and an associate professor of pharmacology, said in a news release.
This gap in understanding is particularly concerning given that recent data indicate women increased their heavy drinking more than men during the pandemic lockdown. Such patterns have heightened the negative health effects of alcohol for women, leading to a rise in hospital visits and complications.
The research team focused on a specific region of the brain known as the bed nucleus of the stria terminalis (BNST). Previous work led by Pleil showed that neurons in this area were more excitable in female mice, correlating with binge drinking behavior. The new study took this a step further by examining the influence of estrogen.
The researchers found that when female mice had high levels of circulating estrogen, their alcohol consumption surged, driven by a spike in neuronal activity in the BNST.
“Estrogen has such powerful effects on so many behaviors, particularly in females,” Pleil added. “So, it makes sense that it would also modulate drinking.”
Surprisingly, the study uncovered that estrogen’s effect on binge drinking occurs through a rapid mechanism. Unlike its usual mode of action, which involves binding to nuclear receptors within cells, estrogen was found to bind to receptors on the surface of neurons. This interaction directly modulates cell-to-cell communication, leading to an immediate increase in drinking behavior.
“We believe this is the first time that anybody has shown that during a normal estrous cycle, endogenous estrogen made by the ovaries can use such a rapid mechanism to control behavior,” added Pleil.
This mechanism was identified to drive the initial, excessive alcohol consumption seen in high-estrogen states.
The findings hold significant implications for potential treatments. By targeting the enzyme that synthesizes estrogens, it might be possible to curb alcohol use. An FDA-approved inhibitor currently used for treating estrogen-sensitive cancers could be repurposed for this new application.
“Combining this drug with compounds that modulate the downstream effects of the chemicals produced by the BNST neurons could potentially provide a new, targeted approach for treating alcohol use disorder,” concluded Pleil.
The discovery paves the way for further research to explore whether similar mechanisms are at play in males, where local conversion of testosterone to estrogen in the brain might affect drinking patterns.
This study not only furthers our understanding of how hormonal fluctuations influence behavior but also sets the stage for targeted, gender-specific interventions to address alcohol use disorders.