# Neural systems mediating the extinction and inhibition of cocaine seeking

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2021 · $442,921

## Abstract

Relapse to cocaine use remains a significant challenge in the treatment of cocaine addiction, yet our
understanding of those neural systems that enable individuals to inhibit cocaine seeking and relapse remains
poor. The long-term goal of our laboratory is to identify the neural circuits and the changes in those circuits that
underlie the inhibition of cocaine-seeking behavior, using rat models of cocaine seeking. The current proposal
builds upon the findings we have obtained in recent years as well as new approaches we have developed in
our laboratory. In our studies, rats undergo cocaine self-administration, extinction training and reinstatement
testing of their cocaine seeking. We have found that the infralimbic cortex is a central component of the
systems involved in the extinction and inhibition of cocaine-seeking behavior. Activity in the infralimbic cortex is
necessary for the normal encoding of the extinction learning as well as extinction expression. For example,
infralimbic activation inhibits cocaine seeking following extinction training. However, the larger circuit in which
the infralimbic cortex performs these functions remains unclear. In particular, as evidence suggests functional
heterogeneity within the infralimbic cortex in terms of its role in cocaine seeking, understanding the larger
circuitry may provide insight into these issues. The proposed work will focus on the specific pathways
projecting into and out of the infralimbic that account for its role in extinction and inhibition of cocaine seeking.
The work will include approaches that have not, to our knowledge, been used in studies of cocaine seeking
and, therefore, will enable notable progress in our knowledge of these systems. In particular, our studies will
use multi-site recordings of neural activity during cocaine seeking to understand how a network of brain
regions coordinates behavior. Moreover, the proposed studies will use optogenetic approaches to examine
how different pathways mediate different aspects of the extinction and inhibition of cocaine seeking. The
findings from this work will reveal those specific pathways and network activity related to the IL with regard to
the extinction/inhibition of cocaine seeking. Furthermore, the proposed work will both 1) examine changes in
IL-based circuits as a consequence of cocaine self-administration and extinction and 2) manipulate these
circuits to determine how they functionally control the inhibition of cocaine seeking. The findings from the
studies will furnish critical new basic knowledge of the neural systems underlying the suppression of cocaine
seeking that will potentially lead to the development of more effective treatments that strengthen such systems
in cocaine-addicted individuals.

## Key facts

- **NIH application ID:** 10215464
- **Project number:** 5R01DA049139-02
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** RYAN T LALUMIERE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $442,921
- **Award type:** 5
- **Project period:** 2020-07-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215464

## Citation

> US National Institutes of Health, RePORTER application 10215464, Neural systems mediating the extinction and inhibition of cocaine seeking (5R01DA049139-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10215464. Licensed CC0.

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