Dopamine D-1 receptor agonists combined with the selective D-2 agonist quinpirole facilitate the expression of oral stereotyped behaviour in rats.
The behaviour of rats was studied after combined treatment with the selective DA D-2 agonist quinpirole and three selective D-1 agonists (SK & F 38393, SK & F 75670 and Lu 24-040). The effects on behaviour were compared with those on receptor binding and adenylate cyclase (AC). While the D-1 agonists alone did not induce stereotyped behaviour, quinpirole induced dose-dependent hyperactivity (locomotion, sniffing, head movements and rearing), whereas licking/biting was absent or seen only occasionally. Combined treatment with quinpirole and a D-1 agonist was followed by dose-dependent licking and occasional biting behaviour. The D-1 agonists had similar efficacies, but SK & F 75670 and Lu 24-040 were more potent than SK & F 38393. The maximal effects of SK & F 38393 plus quinpirole were effectively blocked by either a D-1 antagonist (SCH 23390) or a D-2 antagonist (YM 09151-2) confirming the close relation between D-1 and D-2 receptor sites in the brain. Good correspondence was found between affinities to D-1 receptors [( 3H]SCH 23390 binding) in vitro and the EC50 values for stimulation of AC activity. However, the maximal effects on DA-sensitive AC activity were less for SK & F 75670 and Lu 24-040 than for SK & F 38393. Thus, the results indicate that efficacies in the adenylate cyclase assay are dissociated from those on behaviour. Furthermore, the data indicate that in normal rats D-1 receptors are functionally relevant since D-1 agonists facilitate the expression of oral stereotyped behaviour after combination with a D-2 agonist.
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004873:Ergolines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013239:Stereotyped Behavior / Q000187:drug effects*
D001552:Benzazepines; D004873:Ergolines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000262:Adenylyl Cyclases; D011224:Prazosin