# DAT-Disruptive impact of morphine-related cues on goal-directed behavior

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $196,250

## Abstract

Abstract
DAT18-07 Opiate abuse has become an extremely deadly and costly public health epidemic. The best available
tools for treating opiate addiction are limited and have improved little in recent decades. Innovative research is
therefore needed to spur the development of new therapeutic strategies. Given the complex, multifaceted nature
of addiction, it is crucial to develop selective, well-controlled animal models of the specific psychological
mechanisms that contribute to problematic drug use and relapse, as well as the apathy (i.e., loss of motivation
for adaptive, rewarding activities) that often accompanies long-term drug taking and withdrawal. Clinical studies
have shown that drug-associated cues can bias attention and disrupt cognition, but there has been relatively
little animal research on this subject. We suggest that this cognitive disruption removes an important source of
behavioral control, increasing the probability that decisions will be made impulsively, without fully considering
the consequences of one’s actions. Our proposal will test the hypothesis that opiate-paired contextual cues
transiently disrupt goal-directed decision-making. Our preliminary data provide strong support for this hypothesis
and demonstrate the feasibility of our approach. Aim 1 will extend this work to establish a new behavioral protocol
to characterize the tendency for cues paired with morphine to disrupt rats’ capacity for goal-directed action
selection, which will be assayed using the well-established outcome devaluation task. We will also investigate
two hypotheses about the specific mechanisms that underlie this disruptive behavioral influence of morphine-
paired cues. One possibility is that such cues directly interfere with rats' capacity for goal-directed action by
perturbing dorsomedial striatum (DMS) function, which is known to play a fundamental role in this aspect of
decision making. Alternatively, morphine-paired cues may merely shift the balance in behavioral control from the
DMS to the dorsolateral striatum (DLS), which supports automatic, habitual behavior. We will test these
hypotheses in Aim 1 by investigating how morphine-paired cues impact neuronal activation (c-Fos expression)
within the DMS and DLS. Aim 2 will investigate these accounts further using a chemogenetic approach to
selectively inhibit DMS or DLS neurons at test. This will allow us to determine if DLS inactivation restores goal-
directed action selection (and associated DMS neural activation) when morphine-paired cues are present. Our
findings will improve understanding of the specific psychological and neural mechanisms of behavioral
dysregulation caused by opiate cue exposure, and may guide future efforts to develop more targeted strategies
for combating opiate addiction. This work will also serve as the foundation for a separate R01 proposal to study
the specific neural circuits (and adaptations) mediating this important but poorly understood aspect of addiction.

## Key facts

- **NIH application ID:** 10129331
- **Project number:** 5R21DA050116-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Briac Halbout
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,250
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129331

## Citation

> US National Institutes of Health, RePORTER application 10129331, DAT-Disruptive impact of morphine-related cues on goal-directed behavior (5R21DA050116-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10129331. Licensed CC0.

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