A subchronic history of binge-drinking elicits mild, age- and sex-selective, affective, and cognitive anomalies in C57BL/6J mice

C Leonardo Jimenez Chavez; Eliyana Van Doren; Gavin Scheldrup; Emely Rivera; Jose Torres-Gonzalez; Jessica N Herbert; Christopher J E Denning; Sarah Khorsandi; Andrew Garcia; Marian Castro; Karen K Szumlinski

doi:10.3389/fnbeh.2023.1192076

A subchronic history of binge-drinking elicits mild, age- and sex-selective, affective, and cognitive anomalies in C57BL/6J mice

Front Behav Neurosci. 2023 Aug 3:17:1192076. doi: 10.3389/fnbeh.2023.1192076. eCollection 2023.

Affiliations

¹ Department of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, United States.
² Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, United States.
³ Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, United States.

Abstract

Introduction: Alcohol abuse is a risk factor for affective and cognitive disorders, with evidence indicating that adolescent-onset excessive drinking can result in long-term deficiencies in emotional regulation and cognition, with females more susceptible to the negative emotional and cognitive consequences of excessive alcohol consumption. However, our prior examination of the interactions between sex and the age of drinking-onset indicated minimal signs of anxiety-like behavior during alcohol withdrawal, which may have related to the concurrent anxiety testing of male and female subjects.

Methods: The present study addressed this potential confound by assaying for alcohol withdrawal-induced negative affect separately in males and females and expanded our investigation to include measures of spatial and working memory.

Results: Following 14 days of drinking under modified Drinking-in-the-Dark procedures (10, 20, and 40% alcohol v/v; 2 h/day), adolescent and adult binge-drinking mice of both sexes exhibited, respectively, fewer and more signs of negative affect in the light-dark shuttle-box and forced swim tests than their water-drinking counterparts. Adolescent-onset binge-drinking mice also exhibited signs of impaired working memory early during radial arm maze training during early alcohol withdrawal. When tested in late (30 days) withdrawal, only adult female binge-drinking mice buried more marbles than their water-drinking counterparts. However, adolescent-onset binge-drinking mice exhibited poorer spatial memory recall in a Morris water maze.

Discussion: These findings indicate that a subchronic (14-day) binge-drinking history induces mild, age- and sex-selective, changes in negative affect and cognition of potential relevance to understanding individual variability in the etiology and treatment of alcohol abuse and alcohol use disorder.

Keywords: Morris water maze; adolescence; negative affect; radial arm maze; sex differences.

Grants and funding

This research was funded by NIH grant AA024044 (KS; National Institute on Alcohol Abuse and Alcoholism). CJ was supported by an NSF Pre-doctoral Fellowship. ED was supported by UCSB’s EUREKA program.