Repeated administration of cocaine to B6AF1/J mice increased their running response to 20 mg/kg cocaine as much as four-fold over the response to the first injection. After four daily injections, the extent of the increase was proportional to the dose of cocaine that was used for pretreatment. Sensitization persisted for as long as 2 months after the last injection of cocaine. Cocaine-pretreated mice did not show an increased running response to either morphine or d-amphetamine. The response to cocaine was increased two-fold by treatment with morphine and three-fold by pretreatment with d-amphetamine. Pretreatment with either imipramine or reserpine did not produce sensitization to cocaine. There was no correlation between cocaine sensitization and whole-brain catecholamine levels. There were marked differences in both the running response to cocaine and the extent of cocaine sensitization betwee the parental strains, C57B1/6J and A/J. Experiments with recombinant-inbred lines, derived from C57B1/6By and BALB/cBy mice, suggest that the initial response to cocaine and the development of sensitization are controlled by different genetic determinants.

Two progenitor strains, BALB/cBy and C57BL/6By, their reciprocal F1 hybrids, and seven of their recombinant-inbred derived lines were used to examine the genetic basis of the response to thermal pain, and morphine analgesia at doses of 2.5, 5.0 and 10.0mg/kg. Both the latency of response to thermal pain and the analgesic response differed significantly among the various strains tested. Strong genetic determinants appear to control their responses. Analyses of the data did not permit clarification regarding the linkage of these determinants. Photoelectric activity cages were used to test the running response of the same strains to 12.5, 25 and 40 mg/kg morphine sulfate. The genetic determinants for running activity were different from those for analgesia. There is clear evidence for two or more loci controlling the behavior at 60 and 75 min after injection, but not enough information to define the loci involved.

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