Two directions of dopamine D1/D2 receptor interaction in studies of behavioural regulation: a finding generic to four new, selective dopamine D1 receptor antagonists.
A range of new, chemically distinct D1 dopamine receptor antagonists, SCH 39166, NO 756, A-69024 and BW 737C, were studied for their effects on behavioural responses to the selective D2 agonist RU 24213. Each D1 antagonist not only blocked typical sniffing and locomotor responses to RU 24213 but also released atypical myoclonic jerking behaviour, while the selective D2 antagonist YM 09151 blocked these typical responses but did not release jerking. The rank order of effectiveness of these D1 antagonists to release such D2 agonist-induced jerking was similar to that of their selectivities as D1 antagonists; also, the action of BW 737C showed complete enantioselectivity, the inactivity of its R-antipode BW 736C paralleling enantioselective blockade of D1 but not D2 receptors. It appears that while tonic activity through D1 receptors is necessary for the expression of typical D2-stimulated behaviour, via well-known cooperative/synergistic D1:D2 interactions, D1 tone also normally inhibits, via oppositional D1:D2 interactions, the expression of atypical D2-stimulated behaviours such as jerking. Oppositional D1:D2 interactions are evident using all of the classes of selective D1 antagonist currently known, and appear to constitute another general mode of dopaminergic regulation.
Daly
S A
SA
Department of Clinical Pharmacology, Royal College of Surgeons, Dublin, Ireland.
Waddington
J L
JL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010208:Papaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D010627:Phenethylamines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D044005:Tetrahydroisoquinolines
D001552:Benzazepines; D018492:Dopamine Antagonists; D007546:Isoquinolines; D010627:Phenethylamines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D044005:Tetrahydroisoquinolines; C058081:ecopipam; C076525:NO 756; C075318:BW 737C89; C061450:A 69024; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D010208:Papaverine