Genetic evidence that cocaine and caffeine stimulate locomotion in mice via different mechanisms

The effects of cocaine and caffeine on motor activity in two mouse strains 129/OlaHsd (129) and C57BL/6J (C57) were compared. The former mice exhibited lower basal motor activity than the latter. Cocaine (3, 10, 30 mg/kg) injected i.p. in habituated C57 mice produced a dose-dependent increase in rearing, motility and locomotion. In 129 mice, little or no stimulation was seen and only with the highest dose of cocaine. In both strains caffeine (3, 15, 30 mg/kg) produced a dose-dependent increase in rearing, motility and locomotion. The effect of caffeine on rearing was greater in C57 than in 129 mice, but motility and locomotion were stimulated approximately to the same degree in both strains. Thus, differences in the sensitivity to caffeine and cocaine between mouse strains provide genetic evidence that these two stimulants probably produce locomotor stimulation via somewhat different mechanisms.