Recreational use of alcohol can escalate into something more dire such as excessive binge drinking or even an alcohol use disorder. Women are more susceptible than men to these negative effects of alcohol, potentially because of the sex hormone estrogen. A new study from researchers at the University of Illinois at Chicago shows that high estrogen levels may make alcohol more rewarding to female mice. The study, published in the Journal of Neuroscience, suggests that treatment for alcohol use disorder or binge drinking behavior may be more effective if sex differences are considered. Amy Lasek, associate professor of Psychiatry, Anatomy and Cell biology, led the research, which looked specifically at estrogen receptors in the brain to determine the mechanisms by which estrogen regulates alcohol sensitivity. In one experiment, the researchers analyzed post-mortem brain tissue samples from female mice in two reproductive cycle phases: one characterized by high estrogen levels and one characterized by low estrogen levels. They activated estrogen receptors and tracked how dopamine neurons responded to alcohol.
This is what head research Dr. Lasek explained: “We found that when one estrogen receptor was activated – the alpha receptor – dopamine neurons fired at increased rates in response to alcohol. The effect was also greater in the tissues taken from mice in high-estrogen phases. This increased neural activity could translate into a greater feeling of pleasure when drinking. And this enhanced feeling of reward may make alcohol abuse, specifically binge drinking behavior, more likely”. In another experiment, the researchers blocked estrogen receptors located in the ventral tegmental area of the brain (the region known to contain dopamine neurons and be associated with drug use) and tracked the behaviors of both female and male mice in the presence of alcohol. They found that reducing the number of estrogen receptors alpha, led to decreased drinking behavior, but only in female mice. This is a novel finding that suggests there may be a sex-specific role of estrogen receptors in the ventral tegmental area when it comes to alcohol use. The team does not fully know how this is connected to dopamine chemistry.
Research over the past 30 years has clearly delineated circuitry involved in different aspects of addiction. Like an electrical circuit, interruption of a key point of the brain pathways involved in the expression of symptoms of alcohol addiction may be sufficient to disrupt the aspects of addiction (craving, for example) that prevent the maintenance of sobriety. The ventral tegmental area (VTA) is known to be important in the mediation of reward and reinforcement of drugs of abuse and natural reinforcers like food. While changes in the VTA induced by alcohol exposure may precede alcohol-induced alteration in other brain areas, the role of dopamine may continue to be significant throughout the course of alcohol use disorders. Disruption of dopamine signaling may be an early event that leads to, or exacerbates, pathology in other brain regions. Furthermore, restoration or amelioration of dopaminergic neurotransmission may help disrupt pathological adaptations to chronic alcohol exposure and withdrawal, as is beginning to be examined in other addictive disorders.
Amy Lasek, Study Lead Researcher and Associate Professor, Department of Psychiatry, Anatomy and Cell Biology, University of Illinois explained the implications behind the discovery: “As we learn more about the role of estrogen in sensitizing the brain to the effects of alcohol, we may be able to develop more tailored treatments for alcohol use disorder or be able to provide better education to women on how drinking may affect them differently during various stages of their reproductive cycle. This is especially important because although more men are diagnosed with alcohol use disorder, more than 5 million women in the USA also suffer from an alcohol use disorder. There is evidence that women transition more rapidly from problematic alcohol drinking to having an alcohol use disorder and suffer from the negative health effects of alcohol, such as increased cancer risk, liver damage, heart disease and brain damage.”
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
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