INTRANIGRAL INJECTIONS OF SCH-23390 INHIBIT AMPHETAMINE-INDUCED ROTATIONAL BEHAVIOR

Rats were given unilateral 6-hydroxydopamine lesions of the nigrostria tal pathway and permanent indwelling cannula were surgically implanted into the non-lesioned side of the brain; cannula were used for direct injections of dopamine antagonists into the pars reticulata region of the non-lesioned substantia nigra. The selective Dl receptor antagoni st, SCH 23390, was injected intranigrally at various concentrations (3 .0, 1.5, 1.0, 0.6, or 0.3 mM) just prior to an intraperitoneal injecti on of amphetamine. SCH 23390 dose-dependently inhibited amphetamine-in duced rotational behavior with the highest doses completely blocking r otational behavior in some animals. An intranigral injection of the se lective D2 receptor antagonist, (-)-sulpiride (1.0 mM), did not produc e a significant reduction in amphetamine-induced rotational behavior w hereas an equivalent molar concentration of SCH 23390 (1.0 mM) produce d a significant 62% reduction in amphetamine-induced rotational behavi or. A concentration of SCH 23390 that produced a 50% reduction in rota tional behavior when injected directly into the substantia nigra was u nable to produce a significant reduction in rotational behavior when i njected directly into the striatum. The effects of intranigral injecti ons of SCH 23390 on apomorphine-induced rotational behavior were direc tly opposite to that observed for amphetamine-induced rotational behav ior; contralateral rotational behavior increased relative to baseline measures. These data support the hypothesis that dopamine release in t he midbrain may act as a neuromodulator of motor behavior, and that Dl receptors play a functional role in this process.