Effects of chronic treatment with selective and nonselective antagonists on the subtypes of dopamine receptors.
The effects of chronic blockade of D-1, D-2, or both subtypes of dopamine receptors on the densities and properties of the D-1 and D-2 subtypes of dopamine receptors were measured in rat brain. Animals were treated with 14 daily injections (i.p.) of the D-1-selective antagonist SCH-23390, the D-2-selective antagonist sulpiride, the nonselective antagonist fluphenazine, or vehicle. Serial 32-microns horizontal sections that included the caudate putamen were cut and alternately assigned to assays for D-1 or D-2 receptors. D-1 receptors were labeled with 3H-SKF-83566 or 3H-SCH-23390, and D-2 receptors were labeled with 3H-spiroperidol. Scatchard analysis was performed on the saturation data measured in the head of the caudate putamen to obtain estimates of receptor density. As expected, administration of the D-1-selective ligand SCH-23390 resulted in an increase in the density of D-1 receptors by approximately 47% and had no significant effect on the density of D-2 receptors. Similarly, administration of the D-2-selective ligand sulpiride resulted in an increase in the density of D-2 receptors by 25% and had no significant effect on the density of D-1 receptors. Thus the subtypes of dopamine receptors appear to be independently regulated after selective blockade. In contrast to the effects observed with selective antagonists, the results obtained with fluphenazine were more complex. Administration of the relatively nonselective antagonist fluphenazine resulted in an increase in the density of D-2 receptors by 51% but had no significant effect on the density of D-1 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
McGonigle
P
P
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.
Boyson
S J
SJ
Reuter
S
S
Molinoff
P B
PB
D000818:Animals; D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D005476:Fluphenazine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology*
D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013134:Spiperone; D013469:Sulpiride; D005476:Fluphenazine