# Glutamatergic basal forebrain neurons in aversion-resistant drinking

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $468,652

## Abstract

Project Summary
 A hallmark of alcohol use disorder is continued seeking and consumption of alcohol despite negative
consequences. Neuroadaptations in corticostriatal projections to nucleus accumbens are critical for the
development of compulsive-like alcohol use behaviors, including in an aversion-resistant drinking model. Yet it
remains unclear how potentiated activity in nucleus accumbens neurons alters sensitivity to aversive outcomes
during consumption and seeking of alcohol. Pre-existing individual differences in aversion-related circuits have
been shown to predict future compulsive-like alcohol consumption. Yet, we are not aware of any
demonstrations of alcohol-induced neuroadaptations in aversion-related circuits that track the development of
aversion-resistant drinking, and that account for the emergence of this compulsive phenotype after alcohol
exposure. Our long-term goal is to identify dynamics changes in the activity of aversion-related neural circuits
that drive the emergence of compulsive alcohol use. Here, we will examine glutamatergic basal forebrain
neurons that project to the lateral habenula. These neurons are found in an anterior-posterior continuum from
the ventral pallidum to the lateral hypothalamus and are targeted by nucleus accumbens inhibitory projection
neurons. We hypothesize that the emergence of aversion-resistant drinking requires selective inhibition of
these neurons during alcohol consumption.
 A crucial first step in our investigation of this circuit is to determine whether the emergence of aversion-
resistant drinking is correlated with cell-type specific alterations in drinking-related neural activity in the
glutamatergic basal forebrain. We will assess this question, and whether these neural correlates are
downstream of nucleus accumbens mechanisms in Aim 1. Our second goal is to examine lateral habenula
glutamate activity dynamics during aversion-resistant drinking. Therefore, our Aim 2 experiments will utilize a
fluorescent glutamate sensor combined with fiber photometry to identify temporally-specific neural correlates of
aversion-resistant drinking. Finally, in Aim 3 we will use chemogenetic approaches to assess the functional
contributions of basal forebrain projections to lateral habenula in aversion-resistant drinking and determine
which inputs to lateral habenula from regions of the glutamatergic basal forebrain most effectively modulate
compulsive alcohol consumption. Together, these experiments will yield novel insights into the neural circuits
mediating compulsive alcohol use, as well as aversion-related constraint of reward-seeking more broadly.

## Key facts

- **NIH application ID:** 10094944
- **Project number:** 1R01AA028770-01
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Jocelyn M Richard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $468,652
- **Award type:** 1
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10094944

## Citation

> US National Institutes of Health, RePORTER application 10094944, Glutamatergic basal forebrain neurons in aversion-resistant drinking (1R01AA028770-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10094944. Licensed CC0.

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