# Corticostriatal processing of alcohol-paired cues in aversion-resistant drinking

> **NIH NIH P60** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $184,043

## Abstract

Project Summary: Corticostriatal processing of alcohol-paired cues in aversion-resistant drinking
(CAPD)
Treatment resistant alcoholism is characterized by a loss of control over drinking where individuals persistently
use in spite of negative consequences. Currently approved treatments for alcoholism (e.g. disulfiram) aim to
reduce drinking by making alcohol consumption aversive. However, this approach is problematic as the
hedonic properties of alcohol may no longer motivate drinking behavior in advanced stages of the disease.
Rather, when drinking has advanced to a stage that is resistant to aversive consequences, the control of
behavior is thought to transition from neural circuits that mediate higher cognitive functions to those that
mediate compulsions and habits. Two prominent factors that influence the transition to this stage of drinking
are history of alcohol use and genetic risk for alcohol abuse (e.g. family history). Preliminary data from Indiana
Alcohol Research Center (IARC) investigators demonstrate that certain rodent models of genetic risk for
excessive drinking also tend to quickly form habits and compulsive behaviors. Therefore, a critical need exists
to understand how alcohol exposure and genetic factors influence the computational properties of brain
regions necessary for the cognitive control of motivated behavior. The long-term goal of this project is to
understand the heritable changes in neural computation that facilitate the transition to a loss of control over
drinking. Following this transition, alcohol associated cues retain extreme incentive motivational properties
even when associated with aversive consequences. A method commonly used to assess aversion resistant
drinking (ARD) in rodents is measuring their willingness to consume alcohol adulterated with a bad taste - the
quinine devaluation procedure. The central hypothesis of this proposal is that the genetic predisposition to
allocate cognitive resources in a stimulus-dependent manner interacts with chronic alcohol use to facilitate
ARD. Electrophysiological recordings will be obtained from the medial prefrontal cortex and ventral striatum of
awake behaving alcohol preferring (P) and Wistars rats performing a Pavlovian cued access drinking
procedure. This approach will allow the representation of alcohol-paired cues to be measured at the individual
neuron and ensemble levels to determine how they are processed differently during ARD. Rigorous statistical
procedures will be use to quantify the representation of alcohol-paired cues in corticostriatal circuits, and how
they are influenced by alcohol history and genetic risk. Aim 1 will examine changes in the representation of
alcohol-paired cues following alcohol exposure to determine if drinking history and genetic risk enhances the
encoding of alcohol-paired cues in corticostriatal circuits. Aim 2 will determine if drinking history and genetic
risk impair the ability of corticostriatal circuits to remap represent...

## Key facts

- **NIH application ID:** 10064092
- **Project number:** 5P60AA007611-34
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Christopher Court Lapish
- **Activity code:** P60 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $184,043
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064092

## Citation

> US National Institutes of Health, RePORTER application 10064092, Corticostriatal processing of alcohol-paired cues in aversion-resistant drinking (5P60AA007611-34). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10064092. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*