Cocaine-Induced Locomotor Activation Differs Across Inbred Mouse Substrains
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Updated: Sep 22, 2025
Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
Christiann H Gaines1,2, Sarah A Schoenrock1, Joseph Farrington1
1Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Abstract:
Cocaine use disorders (CUD) are devastating for affected individuals and impose a significant societal burden, but there are currently no FDA-approved therapies. The development of novel and effective treatments has been hindered by substantial gaps in our knowledge about the etiology of these disorders. The risk for developing a CUD is influenced by genetics, the environment and complex interactions between the two. Identifying specific genes and environmental risk factors that increase CUD risk would provide an avenue for the development of novel treatments. Rodent models of addiction-relevant behaviors have been a valuable tool for studying the genetics of behavioral responses to drugs of abuse. Traditional genetic mapping using genetically and phenotypically divergent inbred mice has been successful in identifying numerous chromosomal regions that influence addiction-relevant behaviors, but these strategies rarely result in identification of the causal gene or genetic variant. To overcome this challenge, reduced complexity crosses (RCC) between closely related inbred mouse strains have been proposed as a method for rapidly identifying and validating functional variants. The RCC approach is dependent on identifying phenotypic differences between substrains. To date, however, the study of addiction-relevant behaviors has been limited to very few sets of substrains, mostly comprising the C57BL/6 lineage. The present study expands upon the current literature to assess cocaine-induced locomotor activation in 20 inbred mouse substrains representing six inbred strain lineages (A/J, BALB/c, FVB/N, C3H/He, DBA/2 and NOD) that were either bred in-house or supplied directly by a commercial vendor. To our knowledge, we are the first to identify significant differences in cocaine-induced locomotor response in several of these inbred substrains. The identification of substrain differences allows for the initiation of RCC populations to more rapidly identify specific genetic variants associated with acute cocaine response. The observation of behavioral profiles that differ between mice generated in-house and those that are vendor-supplied also presents an opportunity to investigate the influence of environmental factors on cocaine-induced locomotor activity.
Insights
Researchers identified significant differences in cocaine-induced responses across 20 inbred mouse substrains. This finding advances the search for genetic and environmental factors contributing to cocaine use disorders (CUD) and potential treatments.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Cocaine use disorders (CUD) represent a significant public health challenge with no FDA-approved treatments.
- Understanding the genetic and environmental factors underlying CUD is crucial for developing effective therapies.
- Rodent models are vital for studying addiction genetics, but traditional methods often fail to pinpoint causal genes.
Purpose of the Study:
- To identify genetic variations influencing cocaine-induced behaviors using diverse inbred mouse substrains.
- To establish a foundation for using reduced complexity crosses (RCC) to rapidly identify CUD-related genetic variants.
- To investigate the impact of environmental factors on cocaine response by comparing in-house and vendor-supplied mice.
Main Methods:
- Assessed cocaine-induced locomotor activity in 20 inbred mouse substrains from six distinct strain lineages.
- Included substrains bred in-house and those obtained from commercial vendors.
- Utilized phenotypic differences between substrains to enable future RCC studies.
Main Results:
- Identified significant differences in cocaine-induced locomotor response among several inbred mouse substrains.
- Demonstrated the potential of these substrain differences for initiating RCC populations.
- Observed distinct behavioral profiles between in-house and vendor-supplied mice, suggesting environmental influences.
Conclusions:
- The study successfully identified novel substrain differences in response to cocaine, paving the way for targeted genetic research.
- These findings support the use of RCC to accelerate the identification of genes contributing to acute cocaine response.
- The observed environmental effects highlight the importance of considering housing and supplier variations in addiction research.
