Binge drinking during adolescence prevents the normal maturation of brain signalling pathways that regulate alcohol sensitivity

Adolescent binge drinking is a risk behaviour associated with the development of neuropsychiatric disorders later in life, but the pathophysiological mechanisms that render the adolescent brain vulnerable to the long-term consequences of heavy alcohol consumption are only partially understood.
Researchers used a mouse model of adolescent binge drinking and focussed on G protein-gated inwardly rectifying potassium (GIRK) channels, a molecular target of both ethanol and activin A (a signalling protein involved in brain development, plasticity, and maturation).
The researchers examined whole-cell recordings from dentate gyrus granule cells (neurons in the hippocampus, a brain region critical for learning, memory and addiction-related behaviours) in brain slices from alcohol-naive mice. They found a striking reversal of the effect of activin A on ethanol-evoked GIRK current as the mice matured: whereas activin A reduced the ethanol response in cells from adult mice, it further lowered the already lower ethanol threshold in cells from young mice. In cells from adult mice with binge drinking-like experience in their youth, the reversal of the activin effect on ethanol-evoked GIRK current with maturation was suppressed, thereby perpetuating the adolescent phenotype of activin-boosted ethanol sensitivity into adulthood. Underscoring the translational significance of an aberrantly enhanced GIRK current response to ethanol, the GABAB receptor agonist baclofen, which is used “off label” to treat alcohol use disorders, suppressed the permanently enhanced GIRK response to ethanol after heavy adolescent drinking.
Binge drinking during adolescence prevents the normal maturation of brain signalling pathways that regulate alcohol sensitivity, leaving the adult brain abnormally responsive to alcohol at the cellular level — a change that can be pharmacologically corrected by baclofen.
Source: Stürzenberger, S., Bülow, N., Kalinichenko, L.S., Licha, R., Eulenburg, V., Dahlmanns, M., Müller, C.P., Zheng, F., & Alzheimer, C. (2026) Heavy adolescent drinking makes the adult brain more vulnerable to ethanol by permanently altering the age-dependent interplay between alcohol, GIRK channels and activin. Molecular Psychiatry, 31(2):1027-1040. doi.org/10.1038/s41380-025-03210-x