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Updated: Jun 16, 2026
Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
Genetic mapping in collaborative cross mouse strains identifies loci that affect initial sensitivity to cocaine
Sarah A Schoenrock1, Christiann H Gaines1, Padam Kumar1
1Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Rationale:
Cocaine use disorder (CUD) is a significant health concern that has devastating impacts on affected individuals and society. There are currently no approved therapies to treat CUD due, in part, to significant gaps in our knowledge about the underlying factors that increase risk. Individual genetic differences contribute to CUD risk. Identifying specific genetic mechanisms that increase risk could reveal novel targets for treatment and prevention.
Objectives:
We identified two Collaborative Cross (CC) strains, CC004/TauUncJ (CC004) and CC041/TauUncJ (CC041), that differ significantly for locomotor response and self-administration of cocaine. In the current study, we used mapping crosses generated from both strains to identify genetic loci that are associated with behavioral responses to cocaine.
Results:
We bred mice from the low (CC041) and high (CC004) responding strains to C57BL/6NJ mice to produce two F2 populations and identify genetic loci that influence locomotor response to cocaine. We identified three significant loci on chromosomes 7, 11 and 14 in the CC041 F2 mapping cross that collectively explain 14% of the phenotypic variance for locomotor response to cocaine. Bioinformatic analyses identified multiple genes on chromosomes 7 and 11 that are genetically plausible, have functional relevance and are suitable for further exploration.
Conclusions:
Genetically defined and phenotypically divergent mouse strains are a useful tool for identifying candidate genes that influence behavioral responses to psychostimulants. Functional and mechanistic analyses of these genes could provide insights into biological processes that increase risk for CUD.
Insights
Genetic differences influence cocaine use disorder (CUD) risk. Researchers identified specific genetic loci linked to cocaine
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Cocaine use disorder (CUD) poses a major public health challenge with limited treatment options.
- Genetic factors significantly contribute to an individual's susceptibility to CUD.
- Understanding genetic risk mechanisms is crucial for developing novel CUD therapies.
Purpose of the Study:
- To identify genetic loci associated with behavioral responses to cocaine.
- To leverage distinct Collaborative Cross (CC) mouse strains with differing cocaine responses for genetic mapping.
Main Methods:
- Cross-breeding of high-responding (CC004) and low-responding (CC041) mouse strains with C57BL/6NJ mice to create F2 mapping populations.
- Analysis of locomotor response to cocaine in F2 populations.
- Bioinformatic analysis to identify candidate genes within significant genetic loci.
Main Results:
- Three significant genetic loci on chromosomes 7, 11, and 14 were identified in the CC041 F2 cross, explaining 14% of variance in cocaine-induced locomotor response.
- Multiple plausible candidate genes with functional relevance were pinpointed on chromosomes 7 and 11.
- This study demonstrates the utility of genetically divergent mouse models in dissecting complex behaviors.
Conclusions:
- Genetically distinct mouse strains are valuable for discovering genes influencing psychostimulant responses.
- Further investigation of identified genes can illuminate biological pathways underlying CUD risk.
- This research provides a foundation for developing targeted CUD prevention and treatment strategies.
