Supersensitivity to a D-1 dopamine receptor agonist and subsensitivity to a D-2 receptor agonist following chronic D-1 receptor blockade.
The effect of chronic D-1 dopamine (DA) receptor blockade on D-1 DA receptors and DA-mediated behaviors was studied in rats with unilateral, quinolinic acid-induced striatal lesions. Administration of the selective D-1 antagonist SCH 23390 for 15 days increased D-1 receptor numbers in the unlesioned striatum as indicated by [125I]SCH 23982 binding; ipsilateral turning initiated by the D-2 receptor agonist LY 171555 decreased, while grooming produced by the D-1 receptor agonist SKF 38393 intensified. There was, however, no change in the ability of the D-1 agonist to potentiate D-2 agonist-mediated rotation. The observed behavioral subsensitivity in response to a D-2 agonist may reflect D-1 receptor upregulation and the consequent imbalance of D-1/D-2 receptor interactions in the striatum where these two receptor subtypes appear to play opposite functional roles; potentiation of grooming, primarily a D-1 receptor-mediated behavior, may also reflect the increase in D-1 receptor numbers.
Barone
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P
Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.
Tucci
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Parashos
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Chase
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000031:analogs & derivatives* / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D018492:Dopamine Antagonists; D004873:Ergolines / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects; D007700:Kinetics; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*
C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D001552:Benzazepines; D018492:Dopamine Antagonists; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine