Higher estrogen levels linked to increased alcohol sensitivity in brain's 'reward center'

November 6, 2017, University of Illinois at Chicago
Amy Lasek, assistant professor of psychiatry, UIC College of Medicine. Credit: Jenny Fontaine.

The reward center of the brain is much more attuned to the pleasurable effects of alcohol when estrogen levels are elevated, an effect that may underlie the development of addiction in women, according to a study on mice at the University of Illinois at Chicago.

Led by Amy Lasek, assistant professor of psychiatry in the UIC College of Medicine, researchers found that in a region of the brain called the ventral tegmental area, or VTA (also known as the ""), fired most rapidly in response to alcohol when their estrogen levels were high. This response, according to their findings published online in the journal PLOS ONE, is mediated through receptors on dopamine-emitting neurons in the VTA.

"When estrogen levels are higher, alcohol is much more rewarding," said Lasek, who is the corresponding author on the paper and a researcher in the UIC Center for Alcohol Research in Epigenetics. "Women may be more vulnerable to the effects of alcohol or more likely to overindulge during certain stages of their cycle when estrogen levels are higher, or may be more likely to seek out alcohol during those stages."

Studies indicate that gender differences in psychiatric disorders, including addiction, are influenced by estrogen, one of the primary female sex hormones. Women are more likely to exhibit greater escalation of abuse of alcohol and other drugs, and are more prone to relapse in response to stress and anxiety.

The VTA helps evaluate whether something is valuable or good. When neurons in this area of the brain are stimulated, they release dopamine—a powerful neurotransmitter responsible for feelings of wellness—and, in large doses, euphoria. When something good is encountered—for example, chocolate—the neurons in the VTA fire more rapidly, enforcing reward circuitry that encodes the idea that chocolate is enjoyable and something to be sought out. Over time, the VTA neurons fire more quickly at the sight, or even thought of, chocolate, explained Lasek. In addiction, VTA neurons are tuned into drugs of abuse, and fire more quickly in relation to consuming or even thinking about drugs, driving the person to seek them out—often at the expense of their own health, family, friends and jobs.

Many animal studies have shown that alcohol increases the firing of dopamine-sensitive neurons in the VTA, but little is known about exactly why this occurs.

Lasek and her colleagues examined the relationship between estrogen, alcohol and the VTA in female mice. They used naturally cycling mice that were allowed to go through their normal estrous cycles, akin to the menstrual cycle in women.

Mice were evaluated to determine when they entered diestrus—the phase in the estrous cycle when estrogen levels are close to their peak.

"In mice in diestrus, estrogen levels increase to about 10 times higher than they are in estrus, the phase in which ovulation occurs and estrogen levels drop," Lasek said.

VTAs were taken from mice in both estrus and diestrus and kept alive in special chambers. Electrodes recorded the activity of individual dopamine-sensitive neurons in the VTA. Next, the researchers added alcohol to the chamber. Activity increased twice as much in neurons from mice in diestrus compared to the response of neurons from mice in estrus.

Lasek and her colleagues then blocked estrogen receptors on dopamine-sensitive neurons in VTA in mice in estrus and diestrus. With the blocker present, the response to alcohol in neurons from mice in diestrus was significantly lower compared with neurons where estrogen receptors remained functional. The blocker reduced the alcohol response to levels seen in mice in estrus. The responses to alcohol in neurons from in estrus were unaffected by the estrogen receptor blocker.

"The increased reward response to alcohol we see when estrogen levels are high is mediated through receptors for estrogen in the VTA," said Mark Brodie, professor of physiology and biophysics in the UIC College of Medicine and a co-author on the paper.

Lasek believes that the increased sensitivity to alcohol in the VTA when peak may play a significant role in the development of addiction in women.

"We already know that binge drinking can lead to lasting changes in the brain, and in women, those changes may be faster and more significant due to the interaction we see between alcohol, the VTA and ," Lasek said. "Binge drinking can increase the risk of developing alcoholism, so women need to be careful about how much alcohol they drink. They should be aware that they may sometimes inadvertently over-consume alcohol because the area of the brain involved in reward is responding very strongly."

Explore further: Researchers reveal connection between female estrogen cycle and cocaine addiction

More information: Bertha J. Vandegrift et al, Estradiol increases the sensitivity of ventral tegmental area dopamine neurons to dopamine and ethanol, PLOS ONE (2017). DOI: 10.1371/journal.pone.0187698

Related Stories

Researchers reveal connection between female estrogen cycle and cocaine addiction

January 10, 2017
Hormonal fluctuations women undergo make them particularly sensitive, compared to men, to the addictive properties of cocaine, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published January ...

Why does prenatal alcohol exposure increase the likelihood of addiction?

July 7, 2017
One of the many negative consequences when fetuses are exposed to alcohol in the womb is an increased risk for drug addiction later in life. Neuroscientists in the University at Buffalo Research Institute on Addictions are ...

Why binge drinking cause binge eating

January 11, 2017
(Medical Xpress)—A team of researchers affiliated with several institutions in the U.K. has found what they believe is the reason why consumption of alcohol leads to hunger pangs and excessive eating. In their paper published ...

Immune system linked to alcohol drinking behaviour

September 15, 2017
Researchers from the University of Adelaide have found a new link between the brain's immune system and the desire to drink alcohol in the evening.

Protein links alcohol abuse and changes in brain's reward center

September 8, 2017
When given access to alcohol, over time mice develop a pattern similar to what we would call "problem drinking" in people, but the brain mechanisms that drive this shift have been unclear. Now a team of UC San Francisco researchers ...

Stressed-out rats consume more alcohol, revealing related brain chemistry

November 4, 2016
Stress, defined broadly, is a well-known risk factor for later alcohol abuse; however, the brain chemistry underlying interactions between stress and alcohol remain largely unknown. Reinforcement of addictive substance use ...

Recommended for you

Sensitive babies become altruistic toddlers

September 25, 2018
Our responsiveness to seeing others in distress accounts for variability in helping behavior from early in development, according to a study published September 25 in the open-access journal PLOS Biology by Tobias Grossmann ...

Scientists reverse a sensory impairment in mice with autism

September 25, 2018
Using a genetic technique that allows certain neurons in the brain to be switched on or off, UCLA scientists reversed a sensory impairment in mice with symptoms of autism, enabling them to learn a sensory task as quickly ...

Immune cell pruning of dopamine receptors may modulate behavioral changes in adolescence

September 25, 2018
A study by MassGeneral Hospital for Children (MGHfC) researchers finds that the immune cells of the brain called microglia play a crucial role in brain development during adolescence, but that role is different in males and ...

Why it doesn't get dark when you blink

September 25, 2018
People blink every five seconds. During this brief moment, no light falls on the retina, yet people continue to observe a stable picture of the environment with no intervals of darkness. Caspar Schwiedrzik and Sandrin Sudmann, ...

Researchers identify new cause of brain bleeds

September 25, 2018
A team of researchers including UCI project scientist Rachita Sumbria, Ph.D. and UCI neurologist Mark J. Fisher, MD have provided, for the first time, evidence that blood deposits in the brain may not require a blood vessel ...

Lung inflammation from childhood asthma linked with later anxiety

September 25, 2018
Persistent lung inflammation may be one possible explanation for why having asthma during childhood increases your risk for developing anxiety later in life, according to Penn State researchers.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.