# A circuit-driven evaluation of the use of physical activity interventions to improve binge-like ethanol drinking

> **NIH NIH K99** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $185,512

## Abstract

Project Summary
Physical activity (PA) is a cornerstone of human health and well-being; however, its implementation as a viable
treatment and preventative option for alcohol use disorders (AUDs) remains understudied. This is underscored
at the social level by the ~26% of adult U.S. citizens that report binge drinking and the mere 3% of citizens who
manage to meet daily U.S. PA guidelines. The NIAAA recognizes the importance of understanding and
promoting the use of PA for treating AUDs. The effects of voluntary PA on preclinical measures of excessive
alcohol intake are mixed. We seek to better evaluate this relationship by addressing the role of voluntary PA in
reducing binge-like ethanol drinking in a unique genetic risk model of drinking to intoxication, the High Drinking
in the Dark (HDID-1) mouse line (Aim 1). Understanding and defining key stages of PA development and
reinforcement may be important for determining its potential as an AUD treatment option. Chronic PA and
alcohol use create neural remodeling across interconnected brain regions belonging to the mesocorticolimbic
system. This neural network comprises of interoceptive brain regions – those responsible for the processing
and translating the internal body state [such as the insula cortex (IC)] - aversion-related brain regions [such as
the basolateral amygdala (BLA)] and brain regions important for reinforcement [i.e., the ventral tegmental area
(VTA)]. Here, we plan to retrogradely trace the nucleus accumbens (NAc) - the central point of convergence for
this system – and determine which neural inputs are engaged at 2- and 4-weeks of wheel-running. Prior wheel-
running work has characterized cFos using slice-based immunohistochemistry, but only in male rodents.
Considering stark sex differences in PA in humans and rodents, this application addresses a major gap in the
literature. cFos immunoreactivity (IR) will be used in combination with a retrograde tracer (rAAV2-retro-GFP) to
reliably characterize and trace the neural inputs to the NAc. We hypothesize that distinct aversion-related NAc
projections (e.g. extended amygdala) will be engaged during acute wheel-running and that regions important
for interoception and reinforcement (such as the IC and NAc) will be engaged following chronic PA. The IC
relays relevant interoceptive information to limbic regions, such as the NAc, and influences motivated
behaviors (like PA and alcohol use). Chemogenetically silencing the IC  NAc circuit has been shown to
increase interoceptive effects of alcohol in rats. To determine the importance of the IC in the reinforcement of
PA, we will test whether chemogenetically silencing or activating the IC  NAc circuit [using designer
receptors exclusively activated by designer drugs (DREADDs)] will modulate voluntary PA at acute and chronic
timepoints. We hypothesize that chemogenetically silencing the IC  NAc projection will increase acute PA
(associated with aversion) and reduce chronic PA (associated ...

## Key facts

- **NIH application ID:** 10888273
- **Project number:** 5K99AA030806-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Kolter Grigsby
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $185,512
- **Award type:** 5
- **Project period:** 2023-08-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888273

## Citation

> US National Institutes of Health, RePORTER application 10888273, A circuit-driven evaluation of the use of physical activity interventions to improve binge-like ethanol drinking (5K99AA030806-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10888273. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*