Sex differences in nucleus accumbens circuitry engaged with binge-like ethanol drinking

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Addiction Research

Background:

• Women progress to Alcohol Use Disorder (AUD) faster than men.
• The nucleus accumbens (NAc) is crucial for regulating alcohol binge drinking.
• Sex differences in brain region engagement during early alcohol use are not well understood.

Purpose of the Study:

• To investigate sex differences in brain regions and NAc inputs engaged during binge-like alcohol drinking.
• To identify neural correlates underlying faster AUD progression in women.

Main Methods:

• Used a viral retrograde tracer and c-Fos expression in mice to map NAc inputs.
• Employed a 4-day Drinking-in-the-Dark task with ethanol or water.
• Analyzed whole-brain activity in 426 brain areas using advanced data and network analysis.

Main Results:

• Ethanol engaged significantly more NAc inputs in female mice compared to males.
• Binge-like drinking females showed increased activity in 129 brain areas versus males.
• Ethanol altered brain network modularity and connectivity in both sexes, more so in males.

Conclusions:

• Early-stage binge-like alcohol drinking engages brain regions and NAc inputs in a sex-specific manner.
• Observed sex differences in neural engagement may contribute to the accelerated development of AUD in women.