Dopamine D1 receptor stimulation but not dopamine D2 receptor stimulation attenuates haloperidol-induced behavioral supersensitivity and receptor up-regulation.
The effect of selective dopamine D1 and D2 receptor agonists on chronic haloperidol-treated rats was studied. Haloperidol treatment produced a 77% increase in apomorphine-induced sterotypy. The administration of the selective dopamine D1 receptor agonist SKF38393 alone or in combination with the selective dopamine D2 receptor agonist quinpirole attenuated the effect of haloperidol. Treatment with quinpirole alone did not have a significant effect on the response to haloperidol. Haloperidol did not modify the number of dopamine D1 receptors but increased that of dopamine D2 receptors. SKF38393 reversed the effect of haloperidol on dopamine D2 receptor binding. Co-administration of SKF38393 and quinpirole did not modify the increase in the number of dopamine D2 receptors induced by chronic treatment haloperidol. The results confirm a dissociation between behavioral supersensitivity and dopamine receptor up-regulation, suggesting that other mechanisms may be involved in the expression of behavioral supersensitivity.
Marin
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Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892.
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
D015259:Dopamine Agents; D004873:Ergolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006220:Haloperidol