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Sex differences in neuronal activation during aversion-resistant alcohol consumption.

Miranda E Arnold¹, Arielle N Butts¹, Theresa R Erlenbach²

¹Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.

Alcohol, Clinical & Experimental Research

|December 27, 2022

Summary

Female mice show greater resistance to alcohol aversion compared to males, with distinct neuronal activation patterns in key brain regions. These findings highlight sex differences in the neurocircuitry of compulsive alcohol consumption.

Keywords:

EtOH Fos activation aversion consumption sex differences

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Area of Science:

Neuroscience
Behavioral Neuroscience
Addiction Research

Background:

Alcohol Use Disorder (AUD) involves continued alcohol consumption despite negative consequences.
Aversion-resistant drinking is modeled in mice using quinine-adulterated alcohol.
Previous studies on aversion-resistant drinking mechanisms focused solely on male subjects.

Purpose of the Study:

To investigate potential sex differences in neuronal activation underlying aversion-resistant alcohol consumption.
To build upon prior findings showing female mice exhibit greater resistance to quinine-adulterated alcohol than males.

Main Methods:

Male and female C57BL/6J mice were given a choice between alcohol and water.
Alcohol was adulterated with increasing quinine concentrations to test aversion resistance.
Neuronal activation was assessed using Fos immunohistochemistry in brain tissue.

Main Results:

Female mice suppressed alcohol intake less than males when faced with quinine adulteration.
Sex differences in neuronal activation were observed in the ventromedial prefrontal cortex (vmPFC), posterior insular cortex (PIC), and ventral tegmental area (VTA).
Males showed higher activation in the vmPFC and PIC, while females exhibited higher activation in the VTA during quinine-adulterated alcohol consumption.

Conclusions:

Females display greater aversion-resistant alcohol intake compared to males.
Distinct sex-based patterns of neuronal activation in specific brain regions are associated with aversion-resistant drinking.
These neurocircuitry differences may contribute to sex-based variations in compulsive alcohol use behaviors.