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Adolescent alcohol exposure disrupts extinction learning and retrosplenial cortex physiology in adult males

Taxier, L. R.; Kooyman, L. S.; Markowitz, S. Y.; Ritchie, J. L.; Wojick, J. A.; Kash, T. L.

2025-10-01 neuroscience
10.1101/2025.09.29.679287 bioRxiv
Show abstract

Adolescent binge drinking can lead to a myriad of issues later in life, including co-occurring diagnoses of Alcohol Use Disorder (AUD) and affective disorders such as post-traumatic stress disorder (PTSD). Although efforts to understand the effects of adolescent alcohol exposure on later health outcomes have unveiled lasting, maladaptive behaviors in adulthood, questions remain about region and cell-type specific mechanisms that drive such effects. Here, we tested the hypothesis that adolescent alcohol exposure would produce lasting alterations in retrosplenial cortex (RSC) function and physiology. In support of this hypothesis, we found that adolescent intermittent ethanol (AIE) vapor exposure resulted in impaired extinction recall of a trace fear memory in adulthood, as well as lasting reductions in intrinsic excitability in adult RSC pyramidal cells. Importantly, these changes were sex-specific, occurring in males but not females. Together, this work suggests that the RSC may be a key, vulnerable locus to adolescent alcohols detrimental effects.

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