# Sex specificity of corticolimbic circuit activity and anxiety-like behavior after alcohol exposure

> **NIH NIH P60** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $256,807

## Abstract

Sex specificity of corticolimbic circuit activity and anxiety-like behavior after alcohol exposure
Alcohol use disorder (AUD) is a complex clinical condition that is commonly associated with other psychiatric
conditions like anxiety and depression. Despite significant differences in the prevalence and experience of AUD
in men and women, few studies have examined the neurobiological mechanisms underlying sex-specific effects
of alcohol on specific brain regions. The prelimbic prefrontal cortex (PrL) and central amygdala (CeA) have been
implicated in both anxiety and alcohol dependence. Our previous work revealed sex-specific differences in PrL
and CeA activity and anxiety-like behavior following chronic ethanol exposure. Alcohol is acutely anxiolytic, but
prolonged exposure produces an anxiogenic phenotype, particularly in withdrawal. The impact of basal anxiety
levels in sex-specific alcohol sensitivity in PrL and CeA and the role of PrL→CeA in sex differences in anxiety-
like behavior following chronic alcohol exposure remains unknown and offers a potential target for improved
understanding of AUD. Preclinical and emerging clinical evidence indicate that the neurosteroid
allopregnanolone may be a potential therapeutic strategy for the treatment of AUDs via actions on GABAA
receptor-mediated inhibitory control. As our previous work demonstrated sex-specific adaptations in inhibitory
control in PrL and CeA, we will also investigate the impact of allopregnanolone on ethanol-induced dysregulation.
We will employ an integrated molecular, cellular electrophysiological, and whole-animal imaging approach to
rigorously examine sex differences in PrL, CeA, and Pr→CeA circuitry and any sex-specific effects in synaptic
transmission, E/I balance, and network activity following chronic ethanol exposure and withdrawal. We will also
assess the impact of allopregnanolone on any sex-specific changes following chronic ethanol exposure as a
potential therapeutic strategy for the treatment of AUD. The results of these studies will provide important
information on sex differences in the activity of PFC and CeA circuits and anxiety-like behavior and
uncover the potential effects of a pharmacological approach to reverse specific circuit dysfunction
following chronic ethanol exposure.

## Key facts

- **NIH application ID:** 10758597
- **Project number:** 5P60AA011605-27
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Melissa A Herman
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $256,807
- **Award type:** 5
- **Project period:** 1997-12-01 → 2027-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758597

## Citation

> US National Institutes of Health, RePORTER application 10758597, Sex specificity of corticolimbic circuit activity and anxiety-like behavior after alcohol exposure (5P60AA011605-27). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10758597. Licensed CC0.

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