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 V_max 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 μM 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.