# Assessing the contributions of the ventral subiculum to the nucleus accumbens shell projection in a novel ethanol self-administration choice paradigm

> **NIH NIH F31** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2024 · $48,974

## Abstract

PROJECT SUMMARY
The progression of recreational drinking to alcohol use disorder (AUD) is characterized by increased seeking
behavior and loss of intake control, with individuals continuing to use alcohol despite experiencing negative
consequences. While one operant paradigm has been developed to assess operant alcohol self-administration
in a manner that can procedurally separate the appetitive (seeking) vs. consummatory facets of behavior, no
studies have yet leveraged this model to investigate these independent aspects of alcohol self-administration in
the presence of an alternative reinforcer, an astonishing gap in the literature given that six of the eleven
diagnostic criteria of AUD are related to the individual allocating behavior towards alcohol compared to
alternative reinforcers. The paucity of translational models of operant alcohol choice self-administration may
contribute to the continued mystery of the circuitry underlying maladaptive alcohol seeking, precluding the
discovery of therapeutic targets. The present study proposes a novel operant self-administration choice
paradigm which will be used to assess the role that the ventral subiculum of the hippocampus to the nucleus
accumbens shell projection (vSub-NAc) has on alcohol seeking. Preliminary findings from our lab demonstrate
that chemogenetic inhibition of the vSub-NAc produces a uniform reduction in alcohol seeking with minimal
effects on consumption without altering seeking or intake of a sucrose solution in a separate cohort of animals.
Both our lab and others have additionally shown that chronic intermittent ethanol (CIE) not only produces
heightened excitability in vSub, but also results in escalation of seeking and intake. Despite these advances, it
remains unknown how the vSub-NAc projection modulates operant choice behavior when a subject can respond
for ethanol and an alternative reinforcer, whether the behavioral outcome of vSub-NAc inhibition would differ
between CIE-exposed subjects vs. AIR controls, and how sex as a biological variable might mediate these
synaptic and behavioral consequences. Therefore, the overarching goal of this proposal is to implement a
multidisciplinary approach to test the hypotheses that CIE results in reallocation of behavior towards
alcohol and away from an alternative reinforcer via hyperexcitation of the vSub-NAc projection,
suggesting that inhibition of this projection will redirect operant choice behavior towards an alternative
reinforcer. Aim 1 will employ optogenetic techniques to selectively activate or inhibit the vSub-NAc during
alcohol vs. sucrose operant choice self-administration. In Aim 2, we will use CIE as a model of alcohol
dependence coupled with optogenetic circuit manipulations to determine if this circuit has unique behavioral
effects when assessed in alcohol dependent vs. non-dependent subjects. These studies may identify a novel
behavioral mechanism through which the vSub-NAc exerts control over alcohol self-administ...

## Key facts

- **NIH application ID:** 11069499
- **Project number:** 1F31AA032154-01
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Olivia Colarusso
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11069499

## Citation

> US National Institutes of Health, RePORTER application 11069499, Assessing the contributions of the ventral subiculum to the nucleus accumbens shell projection in a novel ethanol self-administration choice paradigm (1F31AA032154-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11069499. Licensed CC0.

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