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.
Peris
J
J
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Zahniser
N R
NR
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005476:Fluphenazine / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013469:Sulpiride; D008012:Lidocaine; D008454:Mazindol; D003042:Cocaine; D001058:Apomorphine; D005476:Fluphenazine; D004298:Dopamine