Chronic antagonist treatment does not alter the mode of interaction of dopamine with rat striatal dopamine receptors.
Chronic treatment with the D1 and D2 dopamine receptor antagonists SCH 23390 (0.5 mg/kg) and haloperidol decanoate (25 mg/kg) caused an up-regulation in D1 and D2 receptor densities, respectively, with no change in KD. Dopamine (20 microM) interacted with both receptor subtypes in a mixed competitive/non-competitive manner, causing a reduction in ligand binding affinity and an apparent decrease in receptor density. In the presence of dopamine, both vehicle-treated and SCH 23390-treated striatal preparations showed a significant loss in affinity for 3H-SCH 23390 binding to D1 receptors and a decrease in D1 receptor density of approximately 26%. Similarly, dopamine caused a substantial loss in 3H-spiperone binding affinity to D2 receptors and a 46% decrease in Bmax in both vehicle-treated and haloperidol-treated membranes. Thus, receptor up-regulation does not appear to alter the mode of interaction of dopamine with rat striatal dopamine receptors.
O'Boyle
K M
KM
Department of Pharmacology, University College Dublin, Belfield, Ireland.
Gavin
K T
KT
Harrison
N
N
D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D006220:Haloperidol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; C033563:haloperidol decanoate; D006220:Haloperidol; D004298:Dopamine