Effects of acute and chronic administration of cocaine on striatal uptake, compartmentalization and release of [3H]dopamine.

The effects of acute and repetitive administration of cocaine were studied on several parameters associated with the uptake and release of [3H]dopamine ([3H]DA) in the striatum. It was found that repetitive administration of cocaine followed 7 days later by acute challenge with cocaine, produced an increase in the Vmax with no change in the affinity of the uptake carrier for either dopamine (DA) or cocaine. The intracellular compartmentalization of [3H]DA in synaptosomes was not altered by either acute or repeated treatment with cocaine. However, chronic administration of cocaine abolished the stimulatory effect that 1 microM amphetamine normally has on the efflux of [3H]DA from the fast pool in untreated synaptosomes. The K(+)-stimulated release of [3H]DA from slices of striatum was not affected by acute or chronically administered cocaine; however, chronically administered cocaine, plus acute challenge with cocaine potentiated the effect of amphetamine on the K(+)-induced release of [3H]DA. This was accompanied by a reduction of the effect of amphetamine on the spontaneous release of DA. In addition, chronically administered cocaine plus acute challenge with cocaine increased K(+)-stimulated release of [14C]acetylcholine [( 14C]ACh). These data suggest that repetitive administration of cocaine, in a regimen that elicits behavioral sensitization, alters the substrates through which amphetamine exerts its effects on the subcellular distribution and release of [3H]DA, and further, that challenge with cocaine of sensitized rats produces a compensatory increase in the uptake of [3H]DA that is correlated with increased depolarization-induced release of [14C]ACh.