# Neuropeptide Y: Role in Ethanol Intake and Sensitivity

> **NIH NIH R37** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $416,034

## Abstract

Project Summary
Alcohol (ethanol) dependence and relapse in abstinent alcoholics are major health problems throughout the
world and neurochemical pathways that modulate these disorders are currently under investigation. However,
the neurobiology underlying binge drinking, a dangerous pattern of behavior that proceeds and contributes to
dependence, has received far less attention. Thus, it is of paramount importance to identify the neurocircuitry
in the brain that modulates binge drinking as such knowledge will provide insight into the initial stages of
alcohol use disorders (AUDs). In the last funding period of this grant we showed that NPY signaling in regions
of the extended amygdala modulate binge-like ethanol drinking via mechanisms that overlap with NPY
mechanisms involved with dependence-like intake. The goal of the present application is to extend our
understanding of the NPY neurocircuitry that modulates binge-like ethanol drinking with a novel focus on NPY
neurocircuitry originating in the medial prefrontal cortex (mPFC). The mPFC provides top-down regulation of
the extended amygdala, in part through a glutamatergic mPFC  basolateral amygdala (BLA) circuit that is
modulated by Y1 receptor (Y1R) signaling. Knowledge obtained from the proposed studies will greatly expand
our understanding of the NPY neurocircuitry that modulates binge-like ethanol intake by linking together
cortical and extended amygdala circuitry. The mPFC integrates information from limbic and cortical regions
and has been implicated in modulating goal-directed (via prelimbic (PL) circuits) and habitual (via infralimbic
(IL) circuits) seeking of ethanol and drugs of abuse, as well as anxiety and fear learning. Recent evidence has
revealed a critical role for NPY signaling in the mPFC, and we have provided strong pilot evidence showing
that infusion of an Y1R agonist into the PL, but not IL, region of the mPFC blunts early-experience binge
drinking, and that chemogenetic silencing of Y1R+ neurons originating from the PL and projecting to the BLA
blunt early-experience binge intake. The proposed aims will use powerful and innovative chemogenetic and
transgenic tools, electrophysiology, and histological approaches to determine if a history of binge-like ethanol
drinking induces alterations of NPY and NPY receptor signaling in the mPFC (Aim 1), if site-directed infusion of
a Y1R agonist or Y2R antagonist, or viral-mediated overexpression of NPY in the mPFC blunts binge-like
ethanol drinking (Aim 2), and if chemogenetic silencing of Y1R+ pyramidal neurons of the mPFC and which
project to the BLA blunt binge-like ethanol intake (Aim 3). Together results from these proposed studies will
address a critical gap in the literature regarding the role of the mPFC, NPY signaling in this region, and the
functional interaction between the mPFC and extended amygdala in the modulation of binge-like ethanol intake
in mice.

## Key facts

- **NIH application ID:** 10130421
- **Project number:** 5R37AA013573-18
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** TODD Eric THIELE
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $416,034
- **Award type:** 5
- **Project period:** 2001-07-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10130421

## Citation

> US National Institutes of Health, RePORTER application 10130421, Neuropeptide Y: Role in Ethanol Intake and Sensitivity (5R37AA013573-18). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10130421. Licensed CC0.

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