Opposing actions of D-1 and D-2 dopamine receptor-mediated alterations of adenosine-3',5'-cyclic monophosphate (cyclic AMP) formation during the amphetamine-induced release of endogenous dopamine in vitro.
Changes in the formation of cyclic AMP following d-amphetamine (0.1 to 20 mumol/l) were examined in vitro in striatal slices of the rat. d-Amphetamine caused a dose-related increase in cyclic AMP content. This action of d-amphetamine was abolished by tissue pretreatment with reserpine (2.5 mg/kg, i.p.) and 3-iodotyrosine (1 mmol/l). By contrast, both clorgyline (0.1 mumol/l) and nomifensine (30 mumol/l) enhanced the d-amphetamine-induced increase in cyclic AMP formation. In superfusion experiments, a strong correlation between endogenous dopamine and cyclic AMP release was observed before, during and after d-amphetamine exposure. Finally, Sch 23390 (10 mumol/l) abolished while (-)sulpiride (10 mumol/l) enhanced the amphetamine-induced increase in cyclic AMP content. These results suggest that d-amphetamine enhances the formation of cyclic AMP through the release of endogenous dopamine into the synapse where it can interact with both D-1 and D-2 dopamine receptors. These results provide direct evidence that the antagonistic properties of D-1 and D-2 receptors on cyclic AMP formation are apparent at striatal synapses during release of endogenous neuronal dopamine.
Azzaro
A J
AJ
Department of Neurology, West Virginia University Medical Center, Morgantown 26506.
Liccione
J
J
Lucci
J
J
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride / Q000494:pharmacology
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013469:Sulpiride; D000242:Cyclic AMP; D003913:Dextroamphetamine; D004298:Dopamine