# Dopamine activity patterns in the medial prefrontal cortex underlying compulsive alcohol drinking in mice

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2022 · $32,002

## Abstract

Project Summary and Abstract
Alcohol use disorder (AUD) is a chronic, relapsing disorder that is profoundly debilitating to those directly
affected while placing enormous economic burden onto society. In the United States, a majority of adults
consume alcohol on a monthly basis yet only a small subset of these individuals will go on to develop AUD,
thus highlighting a critical need to identify risk factors underlying the transition or resilience to problematic
drinking behaviors. Continued use of alcohol despite adverse consequences is a distinguishing feature of AUD
that is mediated, in part, by the medial prefrontal cortex (mPFC). Activity in the mPFC is robustly modulated by
the mesocortical dopamine system, a dopaminergic pathway projecting to the mPFC from the ventral
tegmental area that is believed to influence a wide range of behaviors related to decision-making, response
inhibition, and motivation. Clinical evidence indicates that both pre-existing and alcohol-induced alterations to
the mesocortical dopamine system are critical in the development and maintenance of AUD. However,
preclinical investigations of maladaptive drinking behaviors and their neural correlates involving animal models
have remained predominantly focused on neuroadaptations at specific time points and as a result, often
preclude assessment of pre-existing differences and how these interact with alcohol-induced changes to
produce disparate behavioral outcomes. A main goal of this proposal is to longitudinally monitor real-time
endogenous dopamine release dynamics within-subjects to ultimately identify dopamine release signatures in
the mPFC that are associated with susceptibility to developing AUD-relevant behaviors in mice. To this end,
we will use operant alcohol self-administration, punished alcohol self-administration using quinine adulteration,
and free-access drinking procedures to assess the development of individual differences over multiple
timepoints and drinking experience. Utilizing in vivo fiber photometry in conjunction with a novel dopamine
sensor, we will measure real-time dopamine release in the mPFC throughout these behavioral tests. Further,
using cell-type and projection-specific optogenetics we will directly test the impact of mPFC dopamine system
activity on alcohol self-administration behaviors. Completion of this proposal will provide valuable insight into
the role of mesocortical dopamine system in AUD-relevant behaviors and provide technical and conceptual
training foundational to pursing my goals as an alcohol researcher.

## Key facts

- **NIH application ID:** 10465558
- **Project number:** 1F31AA029626-01A1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Patrick Robert Melugin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $32,002
- **Award type:** 1
- **Project period:** 2022-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10465558

## Citation

> US National Institutes of Health, RePORTER application 10465558, Dopamine activity patterns in the medial prefrontal cortex underlying compulsive alcohol drinking in mice (1F31AA029626-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10465558. Licensed CC0.

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