# Mesocortical neuromodulation in punishment-resistant alcohol drinking

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2022 · $426,959

## Abstract

Project Summary
Long-standing hypotheses have posited a critical role for dysregulated dopaminergic neuromodulation of
prefrontal cortex in the development of alcohol use disorder (AUD). Despite intense interest in the mesocortical
dopamine system, technical challenges have precluded direct, temporally resolved observation of dopamine
release patterns in the prefrontal cortex until recently. Accordingly, questions regarding the basic function of
mesocortical dopamine as well as its role in AUD have been notoriously difficult to address. Here we propose to
use a recently developed genetically-encoded fluorescent dopamine sensor, which allows for direct assessment
of dopamine dynamics in vivo with unprecedented specificity and temporal resolution, to dissect dopamine
release patterns in the medial prefrontal cortex (mPFC) associated with alcohol self-administration behaviors.
In male and female mice, we will first test the responsiveness of dopamine innervation of mPFC to a range of
stimuli including alcohol to determine its contribution to basic behavioral processes. Next we will assess how
these release patterns evolve during initiation of alcohol self-administration and repeated alcohol exposure to
determine if deficits in this system are associated with the emergence of heightened alcohol drinking and
seeking. Finally, we will mechanistically investigate mesocortical control of alcohol drinking behaviors by
manipulating the activity of this system in vivo and determine alcohol’s direct actions on presynaptic dopamine
terminals in the mPFC using ex vivo imaging. Completion of this proposal will provide unprecedented insight and
understanding as to the contribution of dysregulated cortical neuromodulation in AUD-relevant behaviors.

## Key facts

- **NIH application ID:** 10422574
- **Project number:** 1R01AA030115-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Cody Siciliano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $426,959
- **Award type:** 1
- **Project period:** 2022-06-25 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10422574

## Citation

> US National Institutes of Health, RePORTER application 10422574, Mesocortical neuromodulation in punishment-resistant alcohol drinking (1R01AA030115-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10422574. Licensed CC0.

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