A study led by scientists at Weill Cornell Medicine found that the hormone estrogen regulates binge drinking in females, causing them to consume large quantities of alcohol in the first 30 minutes after it’s offered. This behavior, known as “pregaming,” is due to the fact that circulating estrogen increases binge alcohol consumption in females and contributes to known sex differences in alcohol consumption. The study, published in Nature Communications, could lead to novel approaches for treating alcohol use disorder, as females are more susceptible to the negative health effects of alcohol compared to males. Recent studies have shown that women increased their heavy alcohol consumption more than men during the pandemic lockdown, leading to more alcohol-related hospital visits and complications for women.
Researchers found that a specific subpopulation of neurons in the brain region called the bed nucleus of the stria terminalis (BNST) were more excitable in female mice than in males, correlating with their binge drinking behavior. The heightened activity in these neurons in females is believed to be influenced by estrogen, which has powerful effects on many behaviors, particularly in females. The researchers monitored hormone levels throughout the estrous cycle of female mice and found that when estrogen levels were high, females drank much more alcohol compared to when estrogen levels were low. This increased binge drinking behavior was reflected in heightened activity in the BNST neurons, particularly within the first 30 minutes after alcohol was made available, a behavior known as “front-loading.”
Surprisingly, researchers discovered that estrogen’s mechanism of action in promoting binge drinking involved binding to receptors on the neurons’ surface, where it directly modulates cell-cell communication, rather than the typical process of binding to nuclear receptors in the cell nucleus. This rapid action when estrogen levels are high drives the front-loading of alcohol in females. The researchers identified the estrogen receptor responsible for this effect and found that it is expressed in the excited BNST neurons, as well as in neurons from other brain regions that excite them. Further research will investigate the signaling mechanisms for this effect and whether the same system regulates drinking in males.
The researchers believe that inhibiting the enzyme that synthesizes estrogens could offer a novel treatment for selectively reducing alcohol consumption when hormone levels surge. An FDA-approved version of such an inhibitor used to treat women with estrogen-sensitive cancers could potentially be combined with compounds that modulate the downstream effects of chemicals produced by the BNST neurons to provide a targeted approach for treating alcohol use disorder. Dr. Kristen Pleil, the senior author of the study, emphasized the importance of studying alcohol consumption behavior in females and identifying ways to address the negative health effects of alcohol consumption in women. The study findings could lead to new strategies for treating alcohol use disorder, particularly in females.