Selective inactivation of dopamine D1 and D2 receptors in 6-hydroxydopamine-lesioned rats: evidence that the effect of D1 and D2 agonists can be expressed in the absence of the heterologous DA receptor.
EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) markedly decreased the density of dopamine (DA) D1 and D2 receptors in the lesioned and normal striatae of rats lesioned unilaterally with 6-hydroxy-DA. By treatment with either the D1 antagonist SCH 23390 or the D2 antagonist raclopride, together with EEDQ selective inactivation of D2 and D1 receptors, respectively, are obtained. In rats with decreased density of D1 receptors the circling behaviour response to the D1 agonist SK&F 38393 was markedly inhibited 24 hours after EEDQ treatment, whereas the similar response to the D2 agonist pergolide was unchanged. In rats with decreased density of D2 receptors the effects of pergolide and the partial D2 agonist (-)-3-PPP were antagonized, while the effect of SK&F 38393 was unchanged. These results indicate that the effect of D1 and D2 agonists can be expressed in the absence of normal densities of the heterologous DA receptor. In contrast, the responses from homologous DA receptors, mediating the circling behaviour from the denervated side of the brain, are highly sensitive to the inactivating effect of EEDQ.
Arnt
J
J
Department of Pharmacology, H. Lundbeck A/S, Valby, Denmark.
Hyttel
J
J
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists; D006892:Hydroxydopamines / Q000008:administration & dosage*; D008297:Male; D016627:Oxidopamine; D010479:Pergolide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
D001552:Benzazepines; D018492:Dopamine Antagonists; D006892:Hydroxydopamines; D011804:Quinolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D010479:Pergolide; C000470:EEDQ; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine