Intranigral injections of SCH 23390 inhibit amphetamine-induced rotational behavior.

Rats were given unilateral 6-hydroxydopamine lesions of the nigrostriatal 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 D1 receptor antagonist, 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 injection of amphetamine. SCH 23390 dose-dependently inhibited amphetamine-induced rotational behavior with the highest doses completely blocking rotational behavior in some animals. An intranigral injection of the selective D2 receptor antagonist, (-)-sulpiride (1.0 mM), did not produce a significant reduction in amphetamine-induced rotational behavior whereas an equivalent molar concentration of SCH 23390 (1.0 mM) produced a significant 62% reduction in amphetamine-induced rotational behavior. A concentration of SCH 23390 that produced a 50% reduction in rotational behavior when injected directly into the substantia nigra was unable to produce a significant reduction in rotational behavior when injected directly into the striatum. The effects of intranigral injections of SCH 23390 on apomorphine-induced rotational behavior were directly opposite to that observed for amphetamine-induced rotational behavior; contralateral rotational behavior increased relative to baseline measures. These data support the hypothesis that dopamine release in the midbrain may act as a neuromodulator of motor behavior, and that D1 receptors play a functional role in this process.