Phenotypic resolution of spontaneous and D1-like agonist-induced orofacial movement topographies in congenic dopamine D1A receptor 'knockout' mice.
A novel system was used to assess the role of D(1)-like dopamine receptors in distinct topographies of orofacial movements in mice with congenic D(1A) receptor knockout. Under spontaneous conditions, vertical jaw movements in wild-types declined with time at a rate that was reduced in D(1A) mutants, while horizontal jaw movements emerged progressively in wild-types but not in D(1A) mutants; tongue protrusions were absent in D(1A) mutants, while incisor chattering was initially reduced in D(1A) mutants but rose subsequently to reach the level of wild-types. D(1A) receptors exert a topographically specific role in regulating individual spontaneous orofacial movements, and these involve interactions with psychomotor processes which 'sculpt' behavioural change over time. The anomalous D(1)-like agonist SK&F 83959, which fails to stimulate, and indeed inhibits the stimulation of adenylyl cyclase induced by dopamine, readily stimulated vertical jaw movements, tongue protrusions and incisor chattering, and these response topographies were absent in D(1A) mutants. These results suggest that D(1A) receptors may exert some form of permissive role over orofacial topographies initiated via a novel, putative D(1)-like site not linked to adenylyl cyclase, or that some D(1A) receptors might be coupled to a transduction system other than adenylyl cyclase.
Tomiyama
K
K
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, St Stephen's Green, Dublin 2, Ireland,
McNamara
F N
FN
Clifford
J J
JJ
Kinsella
A
A
Drago
J
J
Tighe
O
O
Croke
D T
DT
Koshikawa
N
N
Waddington
J L
JL
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D005152:Facial Muscles / Q000187:drug effects / Q000502:physiology*; D005260:Female; D007180:Incisor / Q000187:drug effects / Q000502:physiology; D007568:Jaw / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009068:Movement / Q000187:drug effects / Q000502:physiology*; D009154:Mutation / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D010641:Phenotype; D017447:Receptors, Dopamine D1 / Q000819:agonists* / Q000172:deficiency / Q000235:genetics*; D014059:Tongue / Q000187:drug effects / Q000502:physiology
D018491:Dopamine Agonists; D010627:Phenethylamines; D017447:Receptors, Dopamine D1; C098593:dopamine D1A receptor; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; C080703:SK&F 83959