Inactivation of dopamine D-1 or D-2 receptors differentially inhibits stereotypies induced by dopamine agonists in rats.
Ex vivo D-1 or D-2 receptor binding in the striatum was reduced by 65-78% after treatment with EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) in combination with either the D-2 antagonist, raclopride, or the D-1 antagonist, SCH 23390, respectively. EEDQ induced a 65% reduction in D-1 receptor binding and a 51% decrease in cAMP production in striatal homogenates. Selective D-2 receptor inactivation inhibited the stereotyped behaviour induced by the mixed D-1/D-2 agonist, apomorphine, or by the D-2 agonist, quinpirole, when given alone and in combination with the D-1 agonist, SK&F 38393. Selective inactivation of D-1 receptors did not inhibit the behavioural effects of quinpirole when given alone and in combination with the D-1 agonists, SK&F 81297, SK&F 38393 or SK&F 75670. Likewise, the effect of apomorphine was unchanged. These results indicate that a normal density of D-2 receptors is critical for the expression of the stereotyped behaviour induced by DA agonists. In contrast, there is a large surplus of D-1 receptors to enable the response to a D-2 agonist. This is particularly illustrated by the persistent behavioural effects of the partial D-1 agonist, SK&F 75670, in rats with up to a 78% decrease in D-1 receptor binding.
Arnt
J
J
Department of Pharmacology, H. Lundbeck A/S, Ottiliavej 7-9, Copenhagen-Valby, Denmark.
Hyttel
J
J
Meier
E
E
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000201:enzymology; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D008297:Male; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects*
D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D000262:Adenylyl Cyclases; D001058:Apomorphine