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Updated: Jun 13, 2026
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Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
Genome-wide association study of cocaine self-administration behavior in Heterogeneous Stock rats
Montana Kay Lara1, Lieselot L G Carrette1, Thiago Missfeldt Sanches1
1Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Nature Communications
|June 11, 2026
Summary
This study identified six genetic loci associated with cocaine use disorder (CUD) in rats, including carboxylesterase genes that metabolize cocaine. These findings offer new biological insights and potential therapeutic targets for CUD.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Cocaine use disorder (CUD) is a significant public health issue with poorly understood genetic underpinnings.
- Identifying genetic factors influencing CUD is crucial for developing effective treatments.
Purpose of the Study:
- To conduct the largest genome-wide association study (GWAS) in rats to identify genes associated with CUD phenotypes.
- To explore genetic correlations between cocaine self-administration, intake escalation, and compulsive-like responding.
Main Methods:
- Utilized a genome-wide association study (GWAS) in N/NIH Heterogeneous Stock rats (n=836).
- Phenotyped rats for cocaine self-administration, intake escalation, and compulsive-like responding.
- Analyzed genetic associations with a stringent genome-wide significance threshold (>-log10(p)=5.58).
Main Results:
- Identified six genome-wide significant loci associated with CUD-related behaviors.
- A key locus on chromosome 19 contains carboxylesterase genes (Ces1c, Ces1d) involved in cocaine metabolism.
- Other identified loci include genes previously linked to substance use disorders (Trak2, Slc10a7, Plcl1, Satb2).
Conclusions:
- This study provides the most extensive genetic analysis of cocaine self-administration in rats to date.
- Replicated previously identified CUD genetic loci and discovered novel associations.
- Highlights the potential of targeting carboxylesterases for pharmacological interventions in CUD treatment.
