Behavioural evidence for "D-1-like" dopamine receptor subtypes in rat brain using the new isochroman agonist A 68930 and isoquinoline antagonist BW 737C.
The full efficacy, high potency isochroman D-1 agonist A 68930 demonstrated greater than 220-fold selectivity for D-1 over D-2 receptors. A 68930 (0.06 and 0.25 mg/kg) readily induced intense grooming, together with vacuous chewing; these responses became less evident following higher doses (1.0 and 4.0 mg/kg) and sniffing became prominent. Intense grooming was blocked by three D-1 antagonists, the benzazepines SCH 23390 (0.01-1.0 mg/kg) and NNC-756 (0.01-1.0 mg/kg), and the isoquinoline BW 737C (0.2-5.0 mg/kg); however, vacuous chewing was not antagonised by SCH 23390 and NNC-756, but was blocked by BW 737C. Intense grooming was attenuated by the D-2 antagonist YM 09151 (0.005-0.5 mg/kg) while vacuous chewing was enhanced. These data suggest that intense grooming is mediated by a "D-1 like" receptor that recognises all known chemical classes of D-1-selective compounds, while vacuous chewing may be mediated by a pharmacologically distinct subtype of "D-1-like" receptor that recognises preferentially the isochromans and isoquinolines.
Daly
S A
SA
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin.
Waddington
J L
JL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects*; D002839:Chromans / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D006120:Grooming / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000187:drug effects*; D013134:Spiperone / Q000493:pharmacokinetics; D013239:Stereotyped Behavior / Q000187:drug effects; D044005:Tetrahydroisoquinolines
D001552:Benzazepines; D002839:Chromans; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007546:Isoquinolines; D017447:Receptors, Dopamine D1; D044005:Tetrahydroisoquinolines; C075318:BW 737C89; D013134:Spiperone; C065380:A 68930