# Arbitration Between Goal-directed and Habitual Ethanol Seeking by the Nucleus Accumbens Shell.

> **NIH NIH R00** · DREXEL UNIVERSITY · 2020 · $248,987

## Abstract

PROJECT SUMMARY
The development of alcohol use disorders involves a transition to inflexible habitual drug-seeking behavior,
resulting in difficulty regulating or terminating drinking behavior. Ethanol exposure is thought to facilitate the
expression of habitual ethanol seeking, and indeed our own data indicate that chronic intermittent ethanol
exposure (CIE) promotes the expression of this behavior. A growing body of literature suggests that
glutamatergic signaling within corticostriatal circuits is dysregulated across chronic ethanol exposure. In
particular, data suggest that CIE increases extracellular glutamate in the nucleus accumbens shell (NAcS), and
that this effect may be mediated by the loss of presynaptic mGluR2. Despite strong evidence that glutamate
signaling within these circuits mediates behavioral flexibility, little is known regarding how NAcS glutamate
signaling changes across the development of inflexible reward seeking, and further, how alterations in NAcS
glutamate signaling can regulate the expression of actions versus habits. This K99/R00 proposal contains a
comprehensive training and research plan based on the applicant’s preliminary findings that regulation of
glutamate signaling within the NAcS can reverse CIE-induced deficits in goal-directed behavior, directly
implicating NAcS glutamate signaling in response strategy selection. During the mentored portion of the award,
the applicant will receive training in cutting-edge laboratory techniques including multielectrode array (MEA)
recording in awake behaving mice, pharmacogenetics and optogenetics. The candidate will use this training to
test the novel hypothesis that alterations in NAcS glutamate signaling resulting from CIE exposure impair
behavioral flexibility. Aim 1 is designed to confirm the hypothesis that CIE-induced deficits in goal-directed
ethanol seeking can be reversed by mGluR2/3 agonism and to confirm the neuroanatomical locus of this effect.
In Aim 2 we will use MEA recordings to test the hypothesis that acquisition of habitual behavior is accompanied
by changes in neuronal activity in the NAcS, as well as synchrony between the NAcS and structures that send
glutamatergic projections to this brain region, including the infralimbic prefrontal cortex (IfL), the basolateral
amygdala (BLA) and the ventral hippocampus (VH). Aim 3 is designed to test the hypothesis that
pharmacogenetic and optogenetic manipulations of activity within distinct glutamatergic projections to the NAcS
– from the IfL, BLA and VH - alter the expression of habitual ethanol seeking. The results of these experiments
are expected to provide considerable information on the neurobiology of habitual ethanol seeking and to identify
mechanisms through which behavioral flexibility can be restored. We expect that the knowledge gained from
these studies will provide significant insight into the development of alcohol use disorders that will ultimately
inform the generation of novel prevention and t...

## Key facts

- **NIH application ID:** 9828729
- **Project number:** 5R00AA024499-05
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** JACQUELINE M BARKER
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,987
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828729

## Citation

> US National Institutes of Health, RePORTER application 9828729, Arbitration Between Goal-directed and Habitual Ethanol Seeking by the Nucleus Accumbens Shell. (5R00AA024499-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9828729. Licensed CC0.

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