Endogenous dopamine functionally activates D-1 and D-2 receptors in striatum.
Rat striatal slices incubated with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine at 1 mM were exposed to different concentrations (1-100 microM) of the catecholamine-releasing drug amphetamine. This produced both a concentration-dependent release of endogenous dopamine and accumulation of cyclic AMP in the slices. The cyclic AMP accumulation due to amphetamine was greatly increased when slices were coincubated with the selective dopamine D-2 antagonist (-)-sulpiride (30 microM), but the amphetamine-induced release of dopamine from the slices was the same in the presence or absence of (-)-sulpiride. Pretreatment of animals with reserpine (5 mg/kg s.c., 18 h before death) and in vitro incubation with alpha-methyl-p-tyrosine (50 microM for 90 min), respectively, reduced the ability of amphetamine (1-100 microM) [in the presence of 30 microM (-)-sulpiride] to induce release of dopamine and to elevate cyclic AMP accumulation in striatal slices. A similar reduction in amphetamine-induced dopamine release and cyclic AMP accumulation in striatal slices was observed 7 days following unilateral 6-OHDA lesions of the medial forebrain bundle of rats. These results suggest that amphetamine induces release of endogenous dopamine from the terminals of nigrostriatal dopamine neurones. Released dopamine is then able functionally and concomitantly to activate D-1 and D-2 receptors, seen as stimulation and inhibition of cyclic AMP accumulation, respectively.
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000032:analysis / Q000502:physiology*; D000242:Cyclic AMP / Q000032:analysis; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006892:Hydroxydopamines / Q000032:analysis; D008297:Male; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D013469:Sulpiride; D016627:Oxidopamine; D000661:Amphetamine; D000242:Cyclic AMP; D004298:Dopamine