Genetic variation in the psychomotor stimulant properties of cocaine in Mus musculus.

Rationale: The psychomotor stimulant properties of drugs are argued to be a key feature of abuse liability. Several studies, primarily using inbred strains of mice, have demonstrated genetic variation in the psychomotor stimulant properties of cocaine. As of yet, however, no gene(s) has been identified which influences this phenotype.

Objectives: The purpose of the present study was to examine a number of inbred strains of mice, including several closely related substrains, for cocaine-induced locomotor activation. Such substrain differences would suggest the possibility of a major gene effect. These data will also help to further characterize the range of genetic variation in response to cocaine.

Methods: Mice from 11 inbred strains were initially injected with saline and activity monitored for 30 min; mice were then removed from the activity monitor, injected with saline or one of six doses of cocaine, and activity was monitored for an additional 30 min.

Results: Compared to several other closely related C57BL substrains, we found the C57BL/10SnJ substrain to be significantly less activated following cocaine administration. In contrast, the C57BR/cdJ and C57L/J substrains showed extremely high levels of cocaine-induced locomotor activation.

Conclusions: The genetic similarity between C57BL/10SnJ and the other closely related C57BL substrains suggests the possibility that the aberrant behavioral response to cocaine observed in B10SnJ mice may be due to a major gene effect. Similarly, the differences found in the C57BR/cdJ and C57L/J substrains may also be influenced by a major gene. The strains examined in this study will be useful tools for identification of relevant quantitative trait loci.