COCAINE DISPOSITION IN DISCRETE REGIONS OF RAT-BRAIN

It has been proposed that various effects of psychoactive drugs on the central nervous system may be related to the capacity of the drug to selectively concentrate in specific regions of the brain. In rat brain , cocaine effects on striatal and nucleus accumbens dopaminergic syste ms show quantitative differences. However, the disposition of cocaine in various brain regions has not been reported. In the present studies we examined the cocaine concentrations over time in serum and discret e brain regions of the rat after single intraperitoneal (i.p.) injecti on. At different time points (5, 10, 20, 30, 60, 120, and 240 min) aft er i.p. injection of cocaine hydrochloride (10 mg kg-1, free base) the rats were decapitated and cocaine in serum and various brain regions was quantitated by a specific gas liquid chromatographic method. There was large inter-individual variability in different rats at each time -point. The disposition pattern of cocaine in rats after i.p. administ ration was similar to that observed in humans after intranasal adminis tration. Initial absorption rate was rapid and, on average, the peak l evels of cocaine were achieved in 10 min. The cocaine levels remained relatively high over the next 50 min indicating continual absorption, and then declined with a rate such that the levels 4 h after cocaine a dministration were undetectable in most of the animals. The overall ch anges in cocaine levels in various brain regions paralleled the serum concentrations. The area under the cocaine concentration-time curve (A UC) revealed more than three-fold differences in cocaine accumulation in various brain regions. This unequal disposition of cocaine may be r esponsible in part for differential biochemical effects in different b rain regions.