# Identification of Genetic Variants that Contribute to Compulsive Cocaine Intakein Rats

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $157,512

## Abstract

Abstract
Our multidisciplinary and highly collaborative consortium identifies gene variants associated with increased
vulnerability to compulsive-like cocaine use by performing the first GWAS using an advanced model of chronic
intravenous cocaine self-administration. We have also created the first preclinical cocaine biobank which enables
researchers who do not have the resources to perform chronic intravenous self-administration or next-generation
genome sequencing to perform advanced genetic, molecular, and cellular studies to further our understanding
of the biological changes underlying addiction-like behaviors. We have obtained results suggesting that it is
critical to add brain and blood samples to measure cocaine levels in rats, however, the rising costs of supplies
and labor threaten the biobank's operations and the overall project. Indeed, our recent GWAS identified a gene,
carboxyl esterase (ces1), encoding an enzyme that degrades cocaine in tissue, but not in blood, underscores
the need for precise measurement of cocaine levels in both the brain and blood, which we did not plan to do in
the parent grant. We identified several coding variants for ces1a, 1c, 1, 1e, and 1g that may alter the ability of
the enzyme to metabolize cocaine. It is critical that we perform additional experiments to test the feasibility of
measuring the pharmacokinetics of cocaine in the brain in vivo within subjects to know if it is possible to expand
the Cocaine Biobank with brain and blood cocaine measurements. This dual measurement is crucial for
understanding individual differences in vulnerability to cocaine addiction. Previous research that relied solely on
blood cocaine levels would have missed significant insights into cocaine pharmacokinetics within the brain.
Therefore, incorporating these measurements into our experimental design is essential to advancing our
understanding of addiction mechanisms and individual vulnerabilities. The overall goal of the following two aims
for this 12-month supplement is to demonstrate the feasibility of integrating brain and blood cocaine
measurements to the biobank using DNA aptamer implanted in the brain and the jugular vein. In Specific Aim 1,
we will gather preliminary data that will allow us to identify individual differences in cocaine pharmacokinetics
between brain and blood in heterogeneous stock rats. In Specific Aim 2, we will ensure the continued viability
and expansion of the Cocaine Biobank, which has become an invaluable resource for addiction research. This
project will continue having a sustained and powerful impact on the field because it provides an exponential
increase in the number of genetic loci identified; establishes the first high-throughput behavioral motifs analysis
of addiction-like behaviors using parallel video-recording and automated machine learning analysis; identifies
novel behavioral endophenotypes of vulnerability/resistance to addiction-like behaviors; and expands and
improves the Co...

## Key facts

- **NIH application ID:** 11128082
- **Project number:** 3U01DA043799-09S2
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Olivier George
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $157,512
- **Award type:** 3
- **Project period:** 2017-04-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11128082

## Citation

> US National Institutes of Health, RePORTER application 11128082, Identification of Genetic Variants that Contribute to Compulsive Cocaine Intakein Rats (3U01DA043799-09S2). Retrieved via AI Analytics 2026-06-04 from https://api.ai-analytics.org/grant/nih/11128082. Licensed CC0.

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