Persistent augmented dopamine release after acute cocaine requires dopamine receptor activation.

Pretreatment of rats with a single injection of cocaine produces a persistent augmentation of amphetamine-induced [3H]dopamine [( 3H]DA) release measured using the in vitro striatal slice preparation. Cocaine has several actions in the nigrostriatal DA system: it blocks DA uptake and thereby indirectly stimulates DA receptors and it also acts as a local anesthetic. We investigated which of these actions is responsible for the augmented amphetamine-stimulated [3H]DA release by determining whether pretreatment with drugs sharing one or more of these actions also augmented release. Release was increased in striatal slices one week after a single injection of either mazindol, a DA uptake blocker and indirect DA receptor agonist, or apomorphine, a direct-acting receptor agonist, whereas the local anesthetic lidocaine had no effect. The prerequisite of DA receptor stimulation was confirmed by pretreatment prior to the cocaine injection with either a nonselective, a D-1 selective or a D-2 selective DA receptor antagonist. Each of these blocked the long-lasting augmentation of release. From these experiments, we conclude that cocaine indirectly activates both D-1 and D-2 DA receptors to produce the persistent augmentation of striatal amphetamine-stimulated [3H]DA release.