# The role of neuronal ensemble Rac1 activity in cocaine seeking behavior

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2024 · $563,694

## Abstract

Project summary/abstract
 Cocaine addiction is a multidimensional psychiatric disorder with pathophysiology that seems to involve
abnormally strong learned associations. These types of learned associations are thought to be encoding within
patterns of sparsely distributed neurons, called neuronal ensembles. Relatively little is known about how
neuronal ensembles controlling cocaine-seeking differ from those underlying natural reward seeking. We have
recently found that a small molecule, Rac1, is differentially expressed in cocaine-paired neuronal ensembles
compared to food-paired ensembles. This molecule may represent a unique molecular adaptation that defines
the cocaine-seeking ensemble. There is, therefore, a critical need to determine the role or Rac1 in cocaine-
seeking ensembles. The long-term goal is to determine the neural mechanisms underlying drug memories to
enable development of clinically useful therapies to alleviate craving and relapse of cocaine use disorder. The
overall objective in this application is to the role of Rac1 in the behavioral, structural, and activity of cocaine-
ensemble neurons. Our central hypothesis is that Rac1 signaling is integral to cocaine-induced
neuroadaptations, driving neuroadaptations that increase the cue-reactivity of cocaine ensemble neurons and
drive cocaine-seeking behavior. The rationale for the proposed research is that understanding how Rac1
expression effects the neuronal ensembles governing cocaine-seeking behavior will provide new opportunities
for developing experimental therapeutics to treating cocaine use disorder. To attain the overall objectives, the
following specific aims will be pursued: 1) Determine the impact of IL ensemble Rac1 activity on cocaine-seeking
behavior; 2) Identify changes in cellular structure within cocaine-associated neuronal ensembles; and 3)
Determine the role of Rac1 activity on cue reactivity of cocaine ensemble neurons. The research proposed in
this application is innovative because it dissects the role of Rac1 within neuronal ensembles in cocaine self-
administration compared to food-seeking ensembles using several cutting-edge methods. These contributions
will have significant impact because they are expected to have determined how Rac1 drives adaptations within
the neuronal ensembles mediating cocaine-seeking.

## Key facts

- **NIH application ID:** 10954035
- **Project number:** 1R01DA059293-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Brandon L Warren
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $563,694
- **Award type:** 1
- **Project period:** 2024-07-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10954035

## Citation

> US National Institutes of Health, RePORTER application 10954035, The role of neuronal ensemble Rac1 activity in cocaine seeking behavior (1R01DA059293-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10954035. Licensed CC0.

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