Dopamine D1 receptors in the sub-commissural part of the globus pallidus and their role in oro-facial dyskinesia in cats.
The possible role of dopamine D1 receptors in the sub-commissural part of the globus pallidus in the induction of oro-facial dyskinesia was studied in cats. The present study reveals two findings. Firstly, bilateral injections of the D1 agonist (+/-)-SK& F38393 into the ventral pallidal area elicited oro-facial dyskinesia, which was quantified in terms of numbers of tongue protrusions. The results show that the dose-effect curve was bell-shaped (1.0, 1.75, 2.5, 5.0 micrograms/0.5 microliters (+/-)-SK&F38393). The oro-facial dyskinesia elicited by (+/-)-SK&F38393 was highly comparable to the oro-facial dyskinesia elicited by injections of the GABA antagonist picrotoxin or the acetylcholine agonist carbachol into the sub-commissural part of the globus pallidus. Secondly, the inactive enantiomer of SK&F38393, i.e. S(-)-SK&F38393, was found to be ineffective in eliciting oro-facial dyskinesia when injected in a dose equivalent to 50% of the most effective dose of the racemic mixture of (+/-)-SK&F38393. Furthermore, the effect elicited by 2.5 micrograms/0.5 microliters (+/-)-SK&F38393 was significantly attenuated by local injection of the D1 antagonist R(+)-SCH23390 in a dose which had no effect itself (1.0 micrograms/0.5 microliters). These findings indicate that the effects elicited by (+/-)-SK&F38393 are D1-specific. The present results thus clearly indicate that dopamine D1 receptors within the sub-commissural part of the globus pallidus are involved in mediating oro-facial dyskinesia in cats.
Spooren
W P
WP
Department of Pharmacology, University of Nijmegen, The Netherlands.
Piosik
P A
PA
Cools
A R
AR
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002415:Cats; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D005145:Face / Q000502:physiology; D005917:Globus Pallidus / Q000502:physiology*; D008297:Male; D009055:Mouth / Q000502:physiology; D009068:Movement / Q000187:drug effects / Q000502:physiology; D010852:Picrotoxin / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000502:physiology*; D017447:Receptors, Dopamine D1; D014059:Tongue / Q000502:physiology
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001552:Benzazepines; D010852:Picrotoxin; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1