Sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J mice

Abstract Background Binge alcohol drinking is a risk factor linked to numerous disease states including alcohol use disorder (AUD). While men binge drink more alcohol than women, this demographic gap is quickly shrinking, and preclinical studies demonstrate that females consistently consume more alc...

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Main Authors: Jean K. Rivera-Irizarry, Lia J. Zallar, Olivia B. Levine, Mary Jane Skelly, Jared E. Boyce, Thaddeus Barney, Ruth Kopyto, Kristen E. Pleil
Format: Article
Language:English
Published: BMC 2023-11-01
Series:Biology of Sex Differences
Online Access:https://doi.org/10.1186/s13293-023-00565-0
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author Jean K. Rivera-Irizarry
Lia J. Zallar
Olivia B. Levine
Mary Jane Skelly
Jared E. Boyce
Thaddeus Barney
Ruth Kopyto
Kristen E. Pleil
author_facet Jean K. Rivera-Irizarry
Lia J. Zallar
Olivia B. Levine
Mary Jane Skelly
Jared E. Boyce
Thaddeus Barney
Ruth Kopyto
Kristen E. Pleil
author_sort Jean K. Rivera-Irizarry
collection DOAJ
description Abstract Background Binge alcohol drinking is a risk factor linked to numerous disease states including alcohol use disorder (AUD). While men binge drink more alcohol than women, this demographic gap is quickly shrinking, and preclinical studies demonstrate that females consistently consume more alcohol than males. Further, women are at increased risk for the co-expression of AUD with neuropsychiatric diseases such as anxiety and mood disorders. However, little is understood about chronic voluntary alcohol drinking and its long-term effects on behavior. Here, we sought to characterize sex differences in chronic binge drinking and the effects of protracted alcohol abstinence on anxiety- and affective-related behaviors in males and females. Methods We assessed binge alcohol drinking patterns in male and female C57BL/6J mice using a modified Drinking in the Dark (DID) paradigm in which mice received home cage access to one bottle of 10% or 20% alcohol (EtOH) or water for 2 h per day on Days 1–3 and to two bottles (EtOH/H2O + H2O) for 24 h on Day 4 for 8 weekly cycles. Mice were then tested for the effects of protracted abstinence on avoidance, affective, and compulsive behaviors. Results Female mice consumed more alcohol than males consistently across cycles of DID and at 2, 4, and 24-h timepoints within the day, with a more robust sex difference for 20% than 10% EtOH. Females also consumed more water than males, an effect that emerged at the later time points; this water consumption bias diminished when alcohol was available. Further, while increased alcohol consumption was correlated with decreased water consumption in males, there was no relationship between these two measures in females. Alcohol preference was higher in 10% vs. 20% EtOH for both sexes. During protracted abstinence following chronic binge drinking, mice displayed decreased avoidance behavior (elevated plus maze, open field, novelty suppressed feeding) and increased compulsive behavior (marble burying) that was especially robust in females. There was no effect of alcohol history on stress coping and negative affective behaviors (sucrose preference, forced swim test, tail suspension) in either sex. Conclusion Female mice engaged in higher volume binge drinking than their male counterparts. Although females also consumed more water than males, their higher alcohol consumption was not driven by increased total fluid intake. Further, the effects of protracted abstinence following chronic binge drinking was driven by behavioral disinhibition that was more pronounced in females. Given the reciprocal relationship between risk-taking and alcohol use in neuropsychiatric disease states, these results have implications for sex-dependent alcohol drinking patterns and their long-term negative neuropsychiatric/physiological health outcomes in humans.
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spelling doaj.art-907eb7c934e8408890615837fc85d7462023-11-19T12:11:23ZengBMCBiology of Sex Differences2042-64102023-11-0114112010.1186/s13293-023-00565-0Sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J miceJean K. Rivera-Irizarry0Lia J. Zallar1Olivia B. Levine2Mary Jane Skelly3Jared E. Boyce4Thaddeus Barney5Ruth Kopyto6Kristen E. Pleil7Neuroscience Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell UniversityPharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell UniversityNeuroscience Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell UniversityDepartment of Pharmacology, Weill Cornell Medicine, Cornell UniversityDepartment of Pharmacology, Weill Cornell Medicine, Cornell UniversityDepartment of Pharmacology, Weill Cornell Medicine, Cornell UniversityPharmacology Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell UniversityNeuroscience Graduate Program, Weill Cornell Graduate School of Medical Sciences, Weill Cornell Medicine, Cornell UniversityAbstract Background Binge alcohol drinking is a risk factor linked to numerous disease states including alcohol use disorder (AUD). While men binge drink more alcohol than women, this demographic gap is quickly shrinking, and preclinical studies demonstrate that females consistently consume more alcohol than males. Further, women are at increased risk for the co-expression of AUD with neuropsychiatric diseases such as anxiety and mood disorders. However, little is understood about chronic voluntary alcohol drinking and its long-term effects on behavior. Here, we sought to characterize sex differences in chronic binge drinking and the effects of protracted alcohol abstinence on anxiety- and affective-related behaviors in males and females. Methods We assessed binge alcohol drinking patterns in male and female C57BL/6J mice using a modified Drinking in the Dark (DID) paradigm in which mice received home cage access to one bottle of 10% or 20% alcohol (EtOH) or water for 2 h per day on Days 1–3 and to two bottles (EtOH/H2O + H2O) for 24 h on Day 4 for 8 weekly cycles. Mice were then tested for the effects of protracted abstinence on avoidance, affective, and compulsive behaviors. Results Female mice consumed more alcohol than males consistently across cycles of DID and at 2, 4, and 24-h timepoints within the day, with a more robust sex difference for 20% than 10% EtOH. Females also consumed more water than males, an effect that emerged at the later time points; this water consumption bias diminished when alcohol was available. Further, while increased alcohol consumption was correlated with decreased water consumption in males, there was no relationship between these two measures in females. Alcohol preference was higher in 10% vs. 20% EtOH for both sexes. During protracted abstinence following chronic binge drinking, mice displayed decreased avoidance behavior (elevated plus maze, open field, novelty suppressed feeding) and increased compulsive behavior (marble burying) that was especially robust in females. There was no effect of alcohol history on stress coping and negative affective behaviors (sucrose preference, forced swim test, tail suspension) in either sex. Conclusion Female mice engaged in higher volume binge drinking than their male counterparts. Although females also consumed more water than males, their higher alcohol consumption was not driven by increased total fluid intake. Further, the effects of protracted abstinence following chronic binge drinking was driven by behavioral disinhibition that was more pronounced in females. Given the reciprocal relationship between risk-taking and alcohol use in neuropsychiatric disease states, these results have implications for sex-dependent alcohol drinking patterns and their long-term negative neuropsychiatric/physiological health outcomes in humans.https://doi.org/10.1186/s13293-023-00565-0
spellingShingle Jean K. Rivera-Irizarry
Lia J. Zallar
Olivia B. Levine
Mary Jane Skelly
Jared E. Boyce
Thaddeus Barney
Ruth Kopyto
Kristen E. Pleil
Sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J mice
Biology of Sex Differences
title Sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J mice
title_full Sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J mice
title_fullStr Sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J mice
title_full_unstemmed Sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J mice
title_short Sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J mice
title_sort sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in c57bl 6j mice
url https://doi.org/10.1186/s13293-023-00565-0
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