TRANSSYNAPTIC EFFECT OF AN INTRASTRIATAL FETAL NIGRAL GRAFT ON THE SENSITIVITY OF THE SUBSTANTIA-NIGRA PARS RETICULATA TO MUSCIMOL IN THE RAT

In the present study, we have investigated the effect of a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway and of a fetal nigral graft in the striatum on circling induced by unilateral microinjection of muscimol in a target structure of the striatum, the substantia nigra pars reticulata. A group of ovariectomized female rats received a unilateral nigral lesion with 6-hydroxydopamine. The lesioned animals were then tested for apomorphine circling (0.25 mg/kg sc). The animals which displayed circling with this drug were divided into two groups with equivalent circling rate. One group received a graft of 1.5 x 10(6) cells taken from the ventral mesencephalon of 14- to 15-day-old rat embryos and the other was kept as control. Six months after the graft, all animals received one microinjection on each side of the GABAergic agonist muscimol (25 ng/0.5 mu l) in site A (rostral part) or in site B (caudal part) of the substantia nigra pars reticulata using indwelling guide cannulae. Circling was monitored during 90 min after the injection. Our results show that: (1) Unilateral degeneration of the nigrostriatal pathway was associated with a decrease of contralateral rotation when muscimol was injected in site A (rostral part) and an increase when administrated in site B (caudal part) of the substantia nigra pars reticu lata on the lesioned side compared to the intact side. (2) A fetal nigral graft implanted into the striatum can normalize the changes in GABAergic sensitivity in site A but not in site B of the substantia nigra pars reticulata. (C) 1994 Academic Press, Inc.