Summary: New research shows that adolescent binge drinking can impair working memory and alter prefrontal cortex function. In a mouse model, early voluntary binge drinking produced brain changes and behavioral patterns that correspond with increased risk for alcohol use disorders in adulthood.
Columbia University researchers report that binge drinking during adolescence disrupts prefrontal cortex activity and working memory in a mouse model, offering insight into why teenagers who binge drink are more likely to develop alcohol problems later in life.
The study, led by investigators at Columbia University Irving Medical Center and published July 4 in the Journal of Neuroscience, used a voluntary drinking model in adolescent mice to investigate how binge-level alcohol exposure affects the developing brain. Unlike forced-exposure paradigms that use vapor or injection, this approach lets individual mice choose whether and how much to drink, better mirroring human drinking patterns during adolescence.
“Adolescent brains are still maturing, and that developmental stage can make them particularly vulnerable to the factors that promote alcohol addiction,” says Neil Harrison, PhD, professor of anesthesiology and pharmacology at Columbia University Vagelos College of Physicians and Surgeons. The research team’s goal was to identify specific neuronal changes caused by adolescent binge drinking that could serve as targets for intervention.
Using an intermittent access protocol in which mice had access to alcohol every other day during a developmental window comparable to human adolescence, researchers observed natural variation in consumption. Some mice drank heavily while others consumed very little, a spread the team says parallels human behavior. Mice that drank heavily during adolescence later showed drinking behaviors and cognitive deficits consistent with increased addiction risk.
Key changes were detected in neurons within the prelimbic region of the medial prefrontal cortex (PFC), a brain area crucial for planning, response inhibition, attention, and working memory. The PFC continues to mature into the third decade of life in humans, which may explain why adolescent exposure to alcohol has particularly lasting effects.
Electrophysiological recordings revealed that pyramidal neurons in the PFC of binge-drinking mice showed reduced intrinsic excitability. Specifically, these neurons displayed a more hyperpolarized resting membrane potential, a reduction in the hyperpolarization-activated cation current (Ih), and diminished intrinsic persistent activity—a pattern of firing associated with the maintenance of information in working memory. These neurophysiological changes correlated with working memory deficits observed in behavioral tests when the mice reached young adulthood.
Many of the changes persisted after a period of abstinence, indicating that adolescent binge exposure can produce sustained alterations in PFC function. The researchers also noted that elements of resting membrane potential and Ih-related responses undergo normal developmental regulation during adolescence, suggesting that alcohol exposure may interrupt the normal maturation trajectory of PFC neurons.
“These alterations in neuronal excitability may help explain why adolescent binge drinkers have trouble with tasks that require working memory and impulse control,” says Michael Salling, PhD, assistant professor of anesthesiology. “Because the observed changes involve ion channel function, targeting those channels could be a strategy to restore normal prefrontal activity and improve cognitive function.”
Behaviorally, the study found that mice exposed to binge-level alcohol during adolescence often showed “front-loading” drinking behavior—consuming alcohol rapidly as soon as it became available—a pattern linked to later alcohol use disorders in humans. Together, the physiological and behavioral findings support the notion that early binge drinking can set the brain on a course that increases vulnerability to addiction.
Funding: Research was supported by grants from the National Institutes of Health (5F32AA022028-02 and 5R01AA023531-04).
Source: Columbia University Irving Medical Center. Report prepared by Helen Garey. Published in the Journal of Neuroscience (July 4).
Original research: The study, titled “Alcohol Consumption during Adolescence in a Mouse Model of Binge Drinking Alters the Intrinsic Excitability and Function of the Prefrontal Cortex through a Reduction in the Hyperpolarization-Activated Cation Current,” was authored by Michael C. Salling, Mary Jane Skelly, Elizabeth Avegno, Samantha Regan, Tamara Zeric, Elcoma Nichols, and Neil L. Harrison. doi: 10.1523/JNEUROSCI.0550-18.2018.
Takeaway: Voluntary adolescent binge drinking in mice produces persistent changes in prefrontal cortical neurons and impairs working memory, offering a plausible biological mechanism for the increased risk of alcohol use disorders observed in humans who begin heavy drinking in their teens. These findings highlight the importance of understanding both the social drivers and the neurobiological consequences of early binge drinking to inform prevention and treatment strategies.