DOPAMINERGIC STIMULATION OF SUBTHALAMIC NUCLEUS ELICITS ORAL DYSKINESIA IN RATS

The effects of dopaminergic stimulation of the subthalamic nucleus (ST h) on motor behavior were examined in conscious rats. Unilateral infus ion of apomorphine (0.1 to 3.2 mu g) into the STh induced a dose-depen dent increase in abnormal, nondirected orofacial movements without alt ering turning, sniffing, grooming, or rearing behaviors. Orofacial mov ements elicited by local infusion of apomorphine (1.0 mu g) into the S Th 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 SC H 23390 (1.0 mu g), but not sulpiride (5.0 mu g), with apomorphine (1. 0 mu g) into the STh blocked oral dyskinesia. Oral movements could not be reelicited by an infusion of apomorphine into the STh after a kain ic acid lesion of the STh. In addition, infusion of apomorphine (1.0 m u g) into sites proximal to but deliberately outside of the STh failed to elicit nondirected oral movements above baseline levels. The resul ts indicate that stimulation of D1 dopaminergic receptors within the S Th induces abnormal orofacial movements. This highlights the importanc e of the dopaminergic input to the STh in the regulation of motor func tion and suggests that D1 receptor antagonists could prove useful in t he treatment of orofacial dyskinesia in humans. (C) 1994 Academic Pres s, Inc.