Acute sensitivity vs. context-specific sensitization to cocaine as a function of genotype.

Individual variability in the acute and chronic effects of psychomotor stimulants is due, in part, to genetic factors. The purpose of this series of studies was to utilize a behavioral model of sensitization, namely increased locomotor activity, to assess individual variability in sensitization to the chronic effects of cocaine and its relationship to the acute stimulant effects of cocaine. Because the degree of sensitization is proportional to the training dose, genetic differences in acute sensitivity to cocaine were assessed and incorporated into the sensitization paradigm. Acute sensitivity and context-dependent sensitization were determined in six inbred mouse strains. Large quantitative and qualitative differences were found in the acute potency and efficacy of cocaine to stimulate locomotor activity. The ED50 was higher in the strains in which cocaine was most efficacious. Context-specific sensitization was determined via chronic administration of equiactive doses of cocaine (ED50) specifically paired with the test apparatus or with the home colony. Sensitization was time, environment, and genotype dependent. The differences in the number of trials required to show sensitization were unrelated to the acute locomotor stimulant effects of cocaine. These findings suggest that acute cocaine-induced locomotor activity and context-specific sensitization reflect different pharmacological properties of cocaine.