# The role of brainstem norepinephrine in binge alcohol drinking and taste aversion

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $349,875

## Abstract

Project Summary/Abstract
Frequent binge drinking has been linked to numerous negative consequences, include and increased risk of
developing ethanol dependence. Thus, it is of paramount importance to identify neuronal mechanisms that
modulate binge drinking as such knowledge will provide insight into novel pharmaceutical treatments that will
protect against this dangerous behavior and the transition to ethanol dependence. Considerable attention has
been paid to the reinforcing effects of ethanol and how these effects motivate ethanol intake. There is strong
evidence that ethanol also entails aversive effects and that these effects, because they are clearly dose
related, can act as a deterrent to overconsumption. One pre-clinical behavioral assay for the aversive effects of
ethanol is the development of a conditioned taste aversion (CTA). When a taste is paired with a treatment
which produces aversive internal symptoms, a strong aversion to the taste develops. Studies comparing
different rodent strains suggest a link between sensitivity to the aversive effects of ethanol and the propensity
to voluntarily ingest ethanol. Importantly, recent data show that mice selectively bred to achieve high blood
ethanol concentrations (BECs) while binge drinking exhibit reduced sensitivity to the aversive properties of
ethanol without alterations in sensitivity to ethanol’s reinforcing properties. Thus, binge-like ethanol drinking in
these mice may be driven by reduced sensitivity to ethanol’s aversive effects. Because the neurocircuitry
underlying the aversive effects of ethanol is still poorly understood, we propose to combine cutting-edged
chemogenetic, molecular, and behavioral tools to characterize the neurocircuitry modulating aversive reactions
to ethanol and binge-like ethanol consumption. Based on previous studies and compelling pilot data, we will
test the novel hypothesis that brainstem norepinephrine (NE) nuclei, specifically the locus coeruleus (LC) and
A2 region (caudal nucleus of the solitary tract; NTS), are activated during binge-like ethanol drinking and serve
as protective mechanisms to “break” ethanol drinking by promoting aversive responses. Specific Aim 1 will use
Designer Receptors Exclusively Activated by Designer Drugs (DREADD) viral vectors to study the role of a NE
circuit from the LC to the rostromedial tegmental nucleus (RMTg) in the modulation of ethanol-induced CTA
and binge-like ethanol consumption, and Aim 2 will use DREADD viral vectors to study the role of a NE circuit
from the A2 region to the lateral parabrachial nucleus (PBN) in the modulation of ethanol-induced CTA and
binge-like ethanol consumption. Aim 3 will use immunohistochemistry and real-time PCR approaches to test
the hypothesis that binge-like ethanol drinking increases NE signaling in the LC and A2, and that this signaling
will become blunted after repeated binge-like drinking episodes, a mechanism that may contribute to the
transition to dependence. As the mechan...

## Key facts

- **NIH application ID:** 10119216
- **Project number:** 5R01AA025809-04
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** TODD Eric THIELE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $349,875
- **Award type:** 5
- **Project period:** 2018-04-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119216

## Citation

> US National Institutes of Health, RePORTER application 10119216, The role of brainstem norepinephrine in binge alcohol drinking and taste aversion (5R01AA025809-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10119216. Licensed CC0.

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