Estrogen Levels May Make Alcohol More Rewarding to Females, Say Authors of Study on Binge-drinking Mice

Changes to levels of the hormone estrogen appear to make consuming alcohol more rewarding to female mice, according to a study. This may mean women are more likely to drink to excess at different phases of the menstrual cycle, one of the scientists involved told Newsweek.

Higher levels of the hormone estrogen have previously been linked to women and rodents drinking more, said the authors of the research published in the journal JNeurosci. Estrogen is thought to change activity in the dopamine system, a collection of cells in the brain that play a part in how we process rewards.

The authors set out to explore how estrogen affects the neurons of mice in a part of the dopamine system called the ventral tegmental area (VTA). They carried out two types of experiments. First, they took brain slices from female mice in either the high or low estrogen phases of their reproductive cycles. Next, they applied alcohol and drugs that block estrogen receptors to the slices and watched to see how dopamine nerve cells would respond.

In their second set of experiments, the scientists injected female and male mice with viruses that reduce the levels of estrogen receptors into the VTA. The mice were then encouraged to drink to the extent that their blood alcohol levels reached those seen in binge-drinking humans, as defined by the U.S. National Institute on Alcohol Abuse and Alcoholism.

The team found that a specific type of receptor enabled estrogen to boost how dopamine neurons responded to alcohol. This may make drinking seem more rewarding in females. In addition, the study showed that lowering levels of estrogen receptors in the VTA caused female mice to drink less alcohol.

Co-author Amy Lasek, associate professor at the Center for Alcohol Research in Epigenetics, University of Illinois at Chicago, told Newsweek: "We were surprised that when we reduced the levels of estrogen receptors in the VTA of male mice, there was no effect on alcohol drinking.

"Estrogen receptors are also present in this region of the brain in male mice, and many studies have demonstrated roles for estrogen receptors in other brain regions in male mice in specific behaviors (sexual behavior and aggression, for instance). So, estrogen receptors in the VTA of female mice are important for promoting binge drinking, but they are not involved in binge drinking in male mice."

She said the research suggests there are different brain mechanisms involved in binge drinking in males and females, and this is important when considering treatments for alcohol use disorder. "Our hope is that a greater understanding of the brain mechanisms that drive excessive drinking will lead to more effective treatments in both sexes," she said.

Targeting estrogen receptors is one option, but drugs that do this have side effects that would outweigh the benefits in healthy women, Lasek said. She hopes future studies will help her team find a targeted approach without negative side effects.

The study was limited because reproductive cycle of mice is not the same as the humans, "although there are some similarities," said Lasek. Like mice, levels of estrogen fluctuate in women different times in their menstrual cycle. Estrogen might be higher during the preovulatory phase, she said.

Women may be more prone to drinking alcohol to excess during this time because they find it more rewarding, and there is some evidence that this is the case, said Lasek. This could put women at greater risk of developing alcohol-related health issues, including drinking problems, she said.

In the U.S., around 9.2 million men and 5.3 million women struggle with alcohol use disorder. However, while the condition affects fewer women, Lasek said they tend to descend more quickly from problem-drinking to having alcohol use disorders.

Ian Hamilton, an expert in drug use and mental health at the Department of Health Sciences at the U.K.'s University of York, who did not work on the study, praised the team for exploring the little-understood relationship between sex and drinking.

He told Newsweek "the magnitude of the relationship [found in the study] between alcohol and females on binge drinking is quite profound."

There is a limit to how much findings from animal studies can be applied to humans, Hamilton said. The setting where a person drinks also "has a significant impact" on the way they drink, their perception of how they feel, and how they behave.

Despite this, he said the findings will be helpful in the future: "This study could really influence and help the way treatment for problems with alcohol is developed and investigated, specifically ensuring that treatment interventions are tailored for females and males,"