Cocaine and its metabolites were measured in plasma and brain from mioe injected ip with cocaine and monitored for sponta-neous locomotor behavior. Cocaine concentrations in the brain reached peak values within 5 mm after administration of cocaine. At all time points between 5 and 60 mm the concentrations of cocaine in the brain were 7-fold higher, on the average, than those in plasma. The opposite was true for the concentrations of benzoylecgonine; brain to plasma ratios of benzoylecgonine were approximately 0.1 from 5 to 30 mm after ip cocaine injection. After ip injection of either 10 or 25 mg/kg of cocaine, cocaine disappeared from plasma and brain with a half-life of 16 mm and benzoylecgonine disappeared from plasma with a halflife of 62 mm. There was good correspondence between locomotor stimulation and concentration of cocaine in the brain measured at 12, 22 and 32 mm after ip administration of 25 mg/kg of cocaine. Among individual animals there was a significant correlation between their locomotor stimulation and their brain cocaine concentration, indicating that differences in cocaine levels in the brain between animals contnbute to their different behavioral response; however, the correlation analysis also indicated the role of other factors determining the locomotor response to cocaine.

For the study of behavioral effects of cocaine in animals, investigators often use rodents and the ip route of administration. Although there is a wealth of information on the dispositional and metabolic profile of cocaine in rodent brain after iv (Misra et a!., 1974; Nayak et at., 1976) and intracisternal(Mule