# The comparative contributions of basolateral amygdala and ventral subiculum inputs to the nucleus accumbens in a novel rodent model of maladaptive alcohol self-administration

> **NIH NIH F31** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $46,752

## Abstract

PROJECT SUMMARY
The progression of recreational drinking to alcohol use disorder is characterized by loss of control over
seeking, which involves continued use of alcohol despite a variety of negative consequences. However, due to
a paucity of translational models for this aspect of alcohol use disorder, little is known about the circuitry
underlying maladaptive alcohol seeking, which precludes the discovery of therapeutic targets. The present
study proposes a novel maladaptive alcohol self-administration task (MAST), which will be used to assess the
role that two distinct neural circuits might play in inhibitory control. Preliminary findings from our lab
demonstrate that chemogenetic inhibition of projections from the basolateral amygdala to the nucleus
accumbens core (BLA-NAcC) or from the ventral subiculum of the hippocampus to the nucleus accumbens
shell (vSub-NAcSh) produces a uniform reduction in appetitive seeking for alcohol with minimal effects on
consumption. Both our lab and others have additionally shown that chronic intermittent ethanol (CIE) not only
produces heightened excitability in the BLA and vSub, but also a behavioral phenotype characterized by
escalation of seeking and intake. Though alcohol seeking is a common and important metric of animal models,
there have been few efforts to parse this construct into more specific facets of motivated behavior. Increased
seeking might result from disinhibition, in which the distinction between appropriate and inappropriate behavior
is known but overridden, or discrimination failure, in which the distinction between when it is appropriate or
inappropriate to drink becomes unclear. Therefore, the proposed studies will employ a multidisciplinary
experimental strategy to test the hypothesis that CIE exposure produces a loss of control over alcohol
seeking and that hyperexcitation of the BLA-NAcC contributes to a behavioral disinhibition phenotype,
while hyperexcitation of the vSub-NAcSh results in discrimination failure. Aim 1 will employ a
chemogenetic technique to selectively activate either the BLA-NAcC or vSub-NAcSh during the MAST. In Aim
2, we will use CIE as a model of alcohol dependence. Behavioral changes will be assessed using the MAST
and alterations in neural activity in the target accumbens-projecting BLA and vSub populations will be
measured by in vivo fiber photometry. These studies may identify a novel behavioral mechanism through which
these circuits exert control over alcohol drinking-related behaviors, with the potential to provide further
evidence that targeting these circuits may have therapeutic value in treating a key behavioral symptom of
alcohol use disorder.

## Key facts

- **NIH application ID:** 10454129
- **Project number:** 5F31AA029292-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Hannah Carlson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-03-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10454129

## Citation

> US National Institutes of Health, RePORTER application 10454129, The comparative contributions of basolateral amygdala and ventral subiculum inputs to the nucleus accumbens in a novel rodent model of maladaptive alcohol self-administration (5F31AA029292-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10454129. Licensed CC0.

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