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

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $786,123

## Abstract

Abstract
The purpose of the NIDA Animal Genetics Program is to identify genetic, genomic, epigenetic variants,
physiology and brain functions that contribute to addiction-like behaviors, related behavioral endophenotypes,
and behavioral comorbidities to substance use disorder. During the past four years, our multidisciplinary and
highly collaborative consortium has been identifying gene variants that are associated with increased
vulnerability to compulsive-like cocaine use by performing the first GWAS using an advanced model of chronic
intravenous cocaine self-administration in N/NIH heterogeneous stock (HS). 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. While these efforts have been very successful in achieving the planned milestones, it has become
clear that our project would benefit from an even larger sample size. In particular, increasing sample sizes lead
to exponential rather than linear increase in the number of loci identified. Moreover, in the past four years there
has been tremendous technological advances in behavioral and genetic analysis that can be leveraged to
provide unprecedented access to identify the single nucleotide and structural variants that contribute to
complex behavioral endophenotypes of high relevance to cocaine use-disorders. The first goal of this
competing renewal is to double the sample size of the current GWAS to increase the number of gene variants
identified and meet the demands of the Biobank. The second goal is to use high-throughput behavioral
phenotyping using markerless pose estimation based on transfer learning with deep neural network to identify
behavioral endophenotypes that can help predict and identify individuals with a resistant, mild, moderate, or
severe phenotype of cocaine addiction-like behaviors. The third goal is to use methodological improvements of
the genetic analysis, including the analysis of structural variants and tandem repeats, as well as enhanced
integration with gene expression data. The fourth goal is to strengthen the cocaine biobank infrastructure. This
project is likely to continue having a sustained and powerful impact on the field because it will provide an
exponential increase in the number of genetic loci identified, eQTLs and PheWAS analysis related to addiction-
like behavior; establish the first high-throughput behavioral motifs analysis of addiction-like behaviors using
parallel video-recording and automated machine learning analysis; identify novel behavioral endophenotypes
of vulnerability/resistance to addiction-like behaviors; and expand and improve the Cocaine Biobank offering
and infrastructure.

## Key facts

- **NIH application ID:** 10694856
- **Project number:** 5U01DA043799-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Olivier George
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $786,123
- **Award type:** 5
- **Project period:** 2017-04-01 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10694856

## Citation

> US National Institutes of Health, RePORTER application 10694856, Identification of Genetic Variants that Contribute to Compulsive Cocaine Intakein Rats (5U01DA043799-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10694856. Licensed CC0.

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