DECREASE OF BEHAVIORAL AND BIOCHEMICAL DENERVATION SUPERSENSITIVITY OF RAT STRIATUM BY NIGRAL TRANSPLANTS

The effect of fetal mesencephalic transplants on dopamine receptor supersensitivity has been studied behaviorally and biochemically in rats with a unilateral lesion of the nigrostriatal pathway. Female rats were lesioned with 6-hydroxydopamine in the left substantia nigra. At least one month later they were tested with apomorphine (0.25 mg/kg, s.c.), amphetamine (5 mg/kg, s.c.), LY 171555 (D2 agonist) (0.5 mg/kg, i.p.) and CY 208243 (D1 agonist) (0.5 mg/kg, s.c.). A suspension containing approximately 1.5 x 10(6) cells from the ventral mesencephalon of rat embryos was distributed in three sites in a triangular fashion in the center of the denervated striatum. Six months later, grafted dopamine neurons reinnervated the medial part of the dorsal striatum, increased the dopamine level and reversed the rotational asymmetry evoked by amphetamine. Apomorphine given four months post-transplant still elicited contraversive circling but the number of turns was reduced. Circling evoked six months post-transplant by CY 208243 or LY 171555 was significantly less in grafted rats than in lesioned non-grafted rats. The density of dopaminergic receptors in the striatum of grafted and lesioned rats was examined by autoradiography by means of in vitro binding with [H-3]SCH 23390 for D1 receptors and [H-3]spiperone for D2 receptors. The results show that intrastriatal nigral transplants decrease the supersensitivity of the D2 receptors and to a lesser extent of the D1 receptors. Normalization of D2 receptors may explain the decrease of behavioral supersensitivity following administration of apomorphine and D2 agonist in grafted rats. D1 receptors were less affected by the lesion and also less normalized than D2 receptors by the transplants. D1 changes localized in other structures of the basal ganglia may explain the decreased circling to apomorphine and D1 agonists in grafted rats.