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 n igral graft in the striatum on circling induced by unilateral microinj ection of muscimol in a target structure of the striatum, the substant ia nigra pars reticulata. A group of ovariectomized female rats receiv ed a unilateral nigral lesion with 6-hydroxydopamine. The lesioned ani mals were then tested for apomorphine circling (0.25 mg/kg sc). The an imals which displayed circling with this drug were divided into two gr oups 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-ol d rat embryos and the other was kept as control. Six months after the graft, all animals received one microinjection on each side of the GAB Aergic agonist muscimol (25 ng/0.5 mu l) in site A (rostral part) or i n site B (caudal part) of the substantia nigra pars reticulata using i ndwelling guide cannulae. Circling was monitored during 90 min after t he injection. Our results show that: (1) Unilateral degeneration of th e nigrostriatal pathway was associated with a decrease of contralatera l 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 sid e. (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 th e substantia nigra pars reticulata. (C) 1994 Academic Press, Inc.