# Project 3: Cocaine IVSA

> **NIH NIH P50** · JACKSON LABORATORY · 2024 · $181,424

## Abstract

PROJECT SUMMARY IVSA (PROJECT 3)
Evidence from both human and animal studies indicates that a multitude of traits, including novelty seeking,
novelty preference, acute drug response, sensitization to drug effects and impulsivity are strongly correlated with
the propensity to develop a substance use disorder. This suggests that there are shared biological mechanism
for these predictive phenomena and drug self-administration. We propose to identify biological mechanisms of
addiction and predisposing behavior by harnessing recent advances in mouse genetic resources including the
genetically diverse Collaborative Cross (CC) reference panel, the high-precision Diversity Outbred (DO) mouse
population, and the computational and statistical methods in systems genetics and integrative genomics
developed to analyze these populations. Project 3 provides critical data for the correlation of multiple risk factors
for vulnerability to cocaine self-administration. We will utilize male and female mice from the inbred CC strains
to quantify genetic correlations among genomics, predisposing novelty-related behaviors and intravenous
cocaine self-administration, as well as their relationship with other heritable addiction-related behaviors assessed
in the Center for Systems Neurogenetics of Addiction (CSNA), which include impulsivity, and cocaine
sensitization. Intravenous drug-self administration (IVSA), considered the gold standard for the assessment of
addiction in preclinical research, will enable quantification of the core features of addiction including compulsive
drug use, difficulty limiting drug intake and an extremely high motivation to take the drug. We will evaluate genetic
correlations among behavioral phenotypes (novelty-related traits, cocaine IVSA) and the expression of genes
and gene networks in CC mice. Gene co-expression networks, QTL positional candidates and behavioral
correlates of gene expression will be compared with other functional genomics data to refine and characterize
candidate genes and biological mechanisms. Behaviorally relevant cocaine response networks will be genetically
mapped in DO mice to independently identify regulatory variants that influence cocaine IVSA and related traits
through transcriptional regulation of other relevant genes. We will use a large population of DO mice to map
behavioral QTLs—and identify candidate genes—that influence cocaine IVSA and predisposing novelty-related
behaviors. The most compelling and tractable of these candidate genes and mechanisms will be validated in
extreme CC strains and newly-engineered mutant mice.

## Key facts

- **NIH application ID:** 10879010
- **Project number:** 5P50DA039841-08
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Elissa J Chesler
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $181,424
- **Award type:** 5
- **Project period:** 2016-08-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879010

## Citation

> US National Institutes of Health, RePORTER application 10879010, Project 3: Cocaine IVSA (5P50DA039841-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10879010. Licensed CC0.

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