SUMMARY: The hormone estrogen boosts neuronal activity in the BNST region of the brain, leading to more binge drinking in women. The impact is especially strong during high-estrogen stages, leading to “front-loading”, or quick alcohol consumption within the first 30 days of supply.
Amazingly, hormone acts rapidly by binding to cell-surface receptor, bypassing conventional gene-altering processes. These results could pave the way for new therapies targeting estrogen’s results to tackle alcohol use disorders, particularly in females.
Important Information:
- Hormonal Influence: Estrogen enhances binge eating by quickly interesting BNST cells.
- Front-Loading Behavior: Females in high-estrogen aspects drink significantly more within 30 days.
- Novel Mechanism: Hormone ties to cell-surface receptors for quick behavioural effects, bypassing slower gene-regulating pathways.
Origin: Weill Cornell University
According to a preliminary study led by researchers at Weill Cornell Medicine, the hormone progesterone regulates binge eating in women, leading them to “pregame” and eat large amounts of alcohol within the first 30 days of receiving it.
The research shows for what is thought to be the first time that females who consuming binge drinking do so and that there are known sex differences in this behavior.
The findings, published Dec. 30 in the journal , Nature Communications, could lead to novel methods for treating alcohol use disorder.
” We know a lot less about what drives alcohol drinking behavior in females because most studies of alcohol use have been done in males”, said senior author , Dr. Kristen Pleil, an associate professor of pharmacology.
Yet females, too, overindulge and are  , more susceptible to the negative health effects , of alcohol than males.
Recent , studies , indicate that, during the pandemic lockdown, women increased their heavy alcohol consumption more than men.
That behavior has important consequences for women’s health, said Dr. Pleil, “because many , studies , show this pattern of drinking enhances alcohol’s harmful effects”. Indeed, women had many more , alcohol-related hospital visits and complications , than men during and since the pandemic.
Estrogen levels at their highest levels are correlated with a rise in alcohol consumption.
Dr. Pleil and her team discovered that a particular subpopulation of neurons in a brain region known as the bed nucleus of the stria terminalis ( BNST ) was more excitable in female mice than male mice in a 2021  study. Their binge drinking behavior was a function of this increased activity.
But what makes this neural circuit in females more excitable?
” Estrogen has such powerful effects on so many behaviors, particularly in females”, Dr. Pleil said. ” So, it makes sense that it would also modulate drinking”.
To assess estrogen’s potential involvement, the researchers, including first author Dr. Lia Zallar, who was a graduate student in the Pleil lab at the time of the research, began by monitoring the hormone levels throughout estrous cycle of female mice.
Then, they served up the alcohol. They discovered that a woman consumes much more alcohol on days when her estrogen level is low than when she has a high level of circulating estrogen.
That increased bingeing behavior was demonstrated by BNST’s increased activity in those same neurons.
” When a female takes her first sip from the bottle containing alcohol, those neurons go crazy”, Dr. Pleil said. ” And if she’s in a high-estrogen state, they go even crazier”.
That extra boost of neural activity means the mice hit the bottle even harder, particularly within the first 30 minutes after the alcohol was made available, a behavior Dr. Pleil refers to as “front-loading”.
Surprising Discovery: Cell-surface Receptors Allow Estrogen to Act Fast
Although the researchers had guessed estrogen might have an impact on drinking, they were surprised by its mechanism of action.
This steroid hormone typically controls behaviors by binding to receptors that travel to the nucleus, changing the activity of specific genes in a process that could take hours.
However, Dr. Pleil and her team realized that when estrogen was injected directly into the BNST, it had already started to excite the neurons and cause binge drinking within minutes.
So the researchers conducted a feat of chemical engineering, led by assistant professor of pharmacology at Weill Cornell Medicine, Dr. Jacob Geri, who had been doctored so it could not enter cells and bind to nuclear receptors.
They determined that when estrogen promotes bingeing, the hormone is binding to receptors on the neurons ‘ surface, where it directly modulates cell-cell communication.
We think this is the first time endogenous estrogen produced by the ovaries can rapidly regulate behavior during a normal estrous cycle, according to Dr. Pleil.
When estrogen is high, that quick action causes the front-loading of alcohol.
The team identified the estrogen receptor that controls this behavior and discovered that it is expressed in both excited BNST neurons and neurons from other brain regions that excite them. The researchers are now looking into the mechanisms that underlie this effect, and they will also look into whether or not the same system controls male drinking.
” All of the infrastructure is there in males, too: the estrogen receptors and the basic circuit organization”, Dr. Pleil said.
The only difference will be the estrogen’s source, which depends on local testosterone-to-estrogen conversion in the brain in males without an ovarian source.
The inhibition of the estrogen-synthetic enzyme might be a novel method for selectively reducing alcohol consumption when hormone levels rise. Women with estrogen-sensitive cancers are currently treated with an FDA-approved version of such an inhibitor.
” A combination of this drug and compounds that modulate the downstream effects of the chemicals produced by the BNST neurons may lead to a new, targeted approach for treating alcohol use disorder,” Dr. Pleil said.
About this news about neuroscience research and binge drinking
Author: Krystle Lopez
Source: Weill Cornell University
Contact: Krystle Lopez – Weill Cornell University
Image: The image is credited to Neuroscience News
Original Research: Open access.
By Kristen Pleil and colleagues,” Rapid nongenomic estrogen signaling controls alcohol-drinking behavior in mice.” Nature Communications
Abstract
In mice, rapid nongenomic estrogen signaling governs drinking behavior.
Ovarian-derived estrogen can signal non-canonically at membrane-associated receptors in the brain to rapidly regulate neuronal function.
Alcohol consumption is more common in women than in men, and binge drinking is associated with high estrogen levels, but it has not been proven that estrogen plays a role in driving alcohol consumption.
When estrogen levels were high during the estrous cycle than when it was low, female mice showed a higher binge drinking rate and a decreased avoidance rate.
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.
This study demonstrates a rapid, nongenomic signaling pathway for ovarian-derived estrogen in the brain that controls behavior in gonadally intact females.
