# Alcohol dependence induced aberrant persistence of reward-seeking and its corticostriatal determinants.

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $37,593

## Abstract

Project Summary
Dysfunctional decision-making is found in alcohol dependence and is hypothesized to involve a shift from initial
goal-directed decision-making to habitual/compulsive control. Top-down, cortical control is essential for goal-
directed decision-making. The pre-SMA/SMA is one such cortical circuit and its activity is disrupted in AUD.
How alcohol dependence affects goal-directed decision-making and the associated cortical neural mechanisms
remains unclear. Goal-directed decision-making is derived from sensitivity to changes in the value of the
consequence (i.e. do I want it) as well as sensitivity to feedback on the decision itself (i.e., was it successful).
While research has focused on the ability for alcohol dependence to induce insensitivity to value change, the
effects of dependence on sensitivity to decision feedback has been neglected. This is a crucial component of
AUD; research into the cortical mechanisms of feedback sensitivity will inform how alcoholics shift from goal-
directed to compulsive control. To assess the role of premotor corticostriatal circuits in alcohol dependence, we
have adapted an operant task in rodents to dissociate value sensitivity from feedback on the decision. Our
preliminary data in mice show chronic alcohol exposure leads to the aberrant persistent use of decision
feedback; CIE exposed mice continue to adjust their behavior to get reward even under circumstances
when control mice do not. Furthermore, chronic alcohol exposure increases the excitability of secondary
motor cortex (M2) pyramidal neurons, which we have shown to be involved when using feedback during
decision-making. Our central hypothesis is that chronic alcohol exposure increases M2 output into DS,
leading to the aberrant persistent use of feedback during decision-making. We will address this
hypothesis by 1) determining how chronic alcohol exposure affects M2 population activity and output to control
decision-making and by 2) manipulating M2 projection neuron activity to establish a causal link between
alcohol dependence-induced changes in M2 activity and persistent feedback control. We will utilize the well-
validated chronic intermittent ethanol vapor exposure to model alcohol dependence, and sophisticated
behavioral analyses combined with in vivo calcium fiber photometry and in vivo chemo- and optogenetics in
order to understand how chronic alcohol exposure affects activity within M2 during goal-directed decision-
making. The pre-SMA/SMA, M2’s human homologue, is associated with response inhibition and is disrupted in
AUD. Since the pre-SMA/SMA is accessible to treatments like TMS, the impact of this work will be to identify a
novel and therapeutically targetable corticostriatal pathway by which chronic alcohol exposure disrupts goal-
directed decision-making.

## Key facts

- **NIH application ID:** 10026015
- **Project number:** 5F31AA027439-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Drew Clinton Schreiner
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,593
- **Award type:** 5
- **Project period:** 2019-08-13 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10026015

## Citation

> US National Institutes of Health, RePORTER application 10026015, Alcohol dependence induced aberrant persistence of reward-seeking and its corticostriatal determinants. (5F31AA027439-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10026015. Licensed CC0.

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