Cocaine levels in striatum and nucleus accumbens: augmentation following challenge injection in rats withdrawn from repeated cocaine administration.

There is general agreement that the brain level of cocaine achieved in response to an intraperitoneal (i.p.) cocaine challenge is higher in animals that have been treated repeatedly with cocaine. However, whether this change in drug disposition persists following withdrawal from repeated treatment is controversial. Rats received either single or repeated injections of cocaine (10 mg/kg, i.p.), and levels of cocaine were measured in dorsal striatum and nucleus accumbens 20 min after the last injection. Cocaine levels were 60-70% higher in both brain regions of rats that had been treated with cocaine once daily for 7 days compared to rats that had received only a single injection. On the 7th day of withdrawal, similar elevations were observed after a challenge injection of cocaine in animals that had been treated repeatedly with cocaine but not in animals that had been treated repeatedly with saline. This persistent pharmacokinetic change should be taken into account in studies of cocaine-induced behavioral sensitization.