Dopaminergic stimulation of subthalamic nucleus elicits oral dyskinesia in rats.
The effects of dopaminergic stimulation of the subthalamic nucleus (STh) on motor behavior were examined in conscious rats. Unilateral infusion of apomorphine (0.1 to 3.2 micrograms) into the STh induced a dose-dependent increase in abnormal, nondirected orofacial movements without altering turning, sniffing, grooming, or rearing behaviors. Orofacial movements elicited by local infusion of apomorphine (1.0 microgram) into the STh were blocked by peripheral administration of the D1 antagonist, SCH 23390 (0.1 mg/kg, sc), but not by the D2 antagonists haloperidol (1.0 mg/kg, sc) or sulpiride (50 mg/kg, sc). Furthermore, coinfusion of SCH 23390 (1.0 microgram), but not sulpiride (5.0 micrograms), with apomorphine (1.0 microgram) into the STh blocked oral dyskinesia. Oral movements could not be reelicited by an infusion of apomorphine into the STh after a kainic acid lesion of the STh. In addition, infusion of apomorphine (1.0 microgram) into sites proximal to but deliberately outside of the STh failed to elicit nondirected oral movements above baseline levels. The results indicate that stimulation of D1 dopaminergic receptors within the STh induces abnormal orofacial movements. This highlights the importance of the dopaminergic input to the STh in the regulation of motor function and suggests that D1 receptor antagonists could prove useful in the treatment of orofacial dyskinesia in humans.
Parry
T J
TJ
Department of Pharmacology, University of Pennsylvania, Philadelphia 19104.
Eberle-Wang
K
K
Lucki
I
I
Chesselet
M F
MF
D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D001552:Benzazepines / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D015259:Dopamine Agents / Q000008:administration & dosage; D004409:Dyskinesia, Drug-Induced / Q000517:prevention & control; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009059:Mouth Diseases / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013469:Sulpiride / Q000008:administration & dosage / Q000494:pharmacology; D013787:Thalamic Nuclei / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
D001552:Benzazepines; D015259:Dopamine Agents; D013469:Sulpiride; D006220:Haloperidol; D001058:Apomorphine; D007608:Kainic Acid