# Chronic alcohol regulates circuitry structure and demand for alcohol

> **NIH NIH R03** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2022 · $80,000

## Abstract

PROJECT SUMMARY
We endeavor to drive new approaches to understand the effect of alcohol on the brain by establishing
fresh mechanisms of action for alcohol exposure on dysregulating novel neurocircuitry. A candidate
circuit altered by alcohol exposure is the downstream synaptic connectivity of the glutamatergic
orbitofrontal cortex (OFC) to nucleus accumbens (NAc) pathway. The goal of this project is to
establish that downstream connectivity of glutamatergic neurons from the OFC to the NAc are altered
by repeated alcohol exposure, which modulates alcohol-driven behavior via dopamine receptor 1-
expressing neurons projecting to the ventral tegmental area (VTA). In this proposal, we will
investigate the neuroanatomical connectivity of the OFC → NAc pathway in the context of alcohol
exposure. Our observations suggest that the OFC → NAc pathway exhibits downstream connectivity
with the VTA of the accumbal direct pathway. This project is based upon the premise that repeated
alcohol exposure will increase excitatory drive of the glutamatergic OFC → NAc pathway onto D1-
expressing NAc → VTA to potentiate motivational effects of alcohol. We hypothesize that repeated
alcohol exposure increases the synaptic connectivity of glutamatergic OFC projections onto
D1-expressing NAc to VTA pathway neurons with concomitant increases in alcohol intake. We
will test this hypothesis with the following specific aims: 1) Define the structural linkage within the
OFC → NAc → VTA circuit after repeated alcohol consumption; and 2) Uncover the behavioral effect
of repeated alcohol exposure on alcohol self-administration. To realize our Aims, we will employ
contemporary strategies such as behavioral economics and transsynaptic neuroanatomical tracing to
detail connectivity through three separate brain regions. Together, the proposed research will
examine alcohol-evoked changes in connectivity as a mechanism that underlies increases in alcohol
taking. Overall, these studies will impact the field by furthering our knowledgebase for understanding
how previous alcohol exposure alters brain circuit connectivity to potentiate future alcohol
consumption.

## Key facts

- **NIH application ID:** 10373655
- **Project number:** 1R03AA029164-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Jonathan Dean Hommel
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $80,000
- **Award type:** 1
- **Project period:** 2022-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373655

## Citation

> US National Institutes of Health, RePORTER application 10373655, Chronic alcohol regulates circuitry structure and demand for alcohol (1R03AA029164-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10373655. Licensed CC0.

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