Locomotor stimulant effects of cocaine and novel cocaine analogs in DBA/2J and C57BL/6J inbred mice.

The current study compared the potencies of cocaine and a series of substituted phenyltropane analogs of cocaine in stimulating locomotor activity in two genetically distinct strains of mice previously shown to differ in their locomotor responsiveness to cocaine. In addition, these compounds were compared for their abilities to induce stereotyped behaviors in naive and cocaine-pretreated mice. All of the analogs tested were more potent locomotor stimulants than cocaine in both strains. Interstrain differences in the locomotor stimulant efficacy of RTI-31 and RTI-98 parallel those of cocaine, with DBA/2J mice being stimulated to a greater extent than C57BL/6J mice at maximally active doses. Significant differences exist in the onset and duration of action among cocaine and several analogs. Whereas the action of cocaine peaks in the first 10 min after injection and thereafter rapidly declines, the stimulant effects of RTI-31, RTI-98, and RTI-113 are maximal at 30-40 min and remain consistent through 60 min postinjection. The current results are discussed in the context of previously published reports of genotype-dependent differences in behavioral responsiveness to cocaine in the DBA/2J and C57BL/6J strains.