# Role of nucleus accumbens core in ethanol reward and binge-like drinking: Focus on sex as a biological variable

> **NIH NIH F31** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $48,974

## Abstract

Project Summary
Binge alcohol drinking is a risk factor for Alcohol Use Disorder (AUD), and while alcohol use and AUD
diagnoses are more prevalent in men than women, this gap has drastically narrowed. Promising therapeutic
candidates for the treatment of AUD have been identified using rodent models; however, few studies have
addressed sex as a biological variable (SABV). Increasing our understanding of SABV in the neural circuitry
that underlies binge-like drinking could lead to more tailored interventions. The nucleus accumbens core
(NAcc) has diverse afferent connections that underlie its crucial involvement in all stages of AUD. In treatment
resistant male patients with AUD, NAcc deep-brain stimulation reduced alcohol craving and promoted either
lower alcohol intake or total abstinence, underscoring the relevance of this brain region in translational AUD
research. In rodents, ethanol (EtOH) drinking increases c-Fos (a biomarker for neuronal activity) in the NAc,
and manipulations of the NAc (via lesion, DBS, or chemogenetics) changes EtOH drinking. Lesioning the NAcc
in male DBA/2J mice prevents acquisition of EtOH conditioned place preference (CPP), a measure of
sensitivity to the rewarding effects of EtOH. Since there are some known sex-differences in the rodent NAcc,
both basally and in response to EtOH, it is imperative to address SABV in studies testing the importance of the
NAcc in EtOH reward and AUD. There are apparent sex differences in EtOH Drinking-in-the-Dark (DID) intake
following chemogenetic manipulation of the NAcc, where inhibition reduces intake in C57BL/6J (B6) males but
increases intake in females. Conversely, stimulation of the NAcc reduces DID EtOH intake in females, with no
effect seen in males. These findings suggest that NAcc manipulation may alter sensitivity to the rewarding
effects of EtOH in a sex-dependent manner, and if so, this could underlie chemogenetically-induced changes
in drinking. Overall, this proposal addresses the importance of the NAcc and SABV in B6 mice during 2
facets of binge/intoxication – 1) how changing NAcc activity impacts the positive subjective effects of
an intoxicating dose of EtOH and 2) determining the NAcc circuitry engaged during binge-like drinking.
Aim 1 tests whether chemogenetic manipulation of the NAcc alters the conditioned rewarding effects of EtOH
using an EtOH conditioned place preference (CPP) task. Aim 2 uses whole-brain imaging to identify regions
engaged during DID (through analysis of c-Fos expression), in combination with use of a viral retrograde tracer
administered into the NAcc. This will allow for quantification of co-labeled c-Fos and GFP-expressing NAcc
inputs to determine which NAcc circuits are engaged during this behavior. Inclusion of both sexes allows us to
determine whether there are differences in c-fos induction, and whether projections to the NAcc are
differentially engaged during DID. The proposed studies will critically improve our understanding of 1) h...

## Key facts

- **NIH application ID:** 10840811
- **Project number:** 5F31AA030908-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Amy Elizabeth Chan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2023-05-09 → 2026-05-08

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840811

## Citation

> US National Institutes of Health, RePORTER application 10840811, Role of nucleus accumbens core in ethanol reward and binge-like drinking: Focus on sex as a biological variable (5F31AA030908-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10840811. Licensed CC0.

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