# Dependence induced dysfunction of decision-making circuits.

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $337,168

## Abstract

Project Summary
Deficits in decision-making underlie numerous components of the addiction cycle including a lack of
behavioral control in daily function as well as compulsive and uncontrollable alcohol consumption and relapse.
In order to understand how these deficits contribute to addiction, it is necessary to understand the basic
decision-making mechanisms disrupted in dependence. One of the key brain regions involved in decision-
making is the orbital frontal cortex (OFC). Despite widespread reports of dependence-induced alterations in
OFC function, relatively little is known in regards to how alcohol dependence affects OFC involvement in
decision-making. At the heart of the problem lies the fact that OFC is widely connected to the rest of the brain
and has been suggested to play a role in numerous behavioral processes. Thus relatively little is known about
specific OFC decision-making processes disrupted in alcohol dependence and the OFC circuits disrupted. This
proposal will use an integrative approach to directly assess effects of alcohol dependence on identified OFC
circuits controlling isolated goal-directed decision-making processes. By combining sophisticated behavioral
tasks with cutting edge cell-type and circuit specific in vivo and ex vivo manipulations and measurements in a
well-validated model of alcohol dependence and alcohol self-administration, this proposal will 1) identify
behavioral mechanisms that contribute to dysfunctional goal-directed decision-making, 2) define the
contributing OFC circuits disrupted in dependence, and 3) determine populations downstream from OFC
controlling the aberrant decision-making observed following dependence. These experiments will test the
central hypothesis that alcohol dependence alters orbital cortex function and output thereby resulting in
dysfunctional value-based decision-making. The proposed studies are expected to significantly advance our
understanding of how alcohol dependence alters decision-making. Insights in to the specific decision-making
and associated neural mechanisms altered are expected to directly lead to testable hypotheses in the
restoration of behavioral control over alcohol consumption and relapse.

## Key facts

- **NIH application ID:** 9965692
- **Project number:** 5R01AA026077-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Christina M. Gremel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $337,168
- **Award type:** 5
- **Project period:** 2017-09-10 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965692

## Citation

> US National Institutes of Health, RePORTER application 9965692, Dependence induced dysfunction of decision-making circuits. (5R01AA026077-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9965692. Licensed CC0.

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