Striatal grafts in rats with unilateral neostriatal lesions--II. In vivo monitoring of GABA release in globus pallidus and substantia nigra

Abstract

GABA release was recorded in vivo by push-pull perfusion from the globus pallidus and substantia nigra of control rats, rats with unilateral ibotenic acid lesions of the neostriatum, and rats with embryonic striatal tissue grafts implanted in the lesioned striatum. The lesions reduced baseline levels of GABA release to 5% of control levels in the globus pallidus and to 13% of control levels in the substantia nigra pars reticulata. GABA release was substantially restored in both the globus pallidus and substantia nigra of the grafted rats, to 34 and 60%, respectively. Peripheral injection of the dopaminergic stimulant methamphetamine induced a short (lasting approximately 20 min) 4-5 fold increase in GABA release in the intact globus pallidus and a longer (lasting longer than 80 min) increase in the substantia nigra. The stimulatory effect of methamphetamine on GABA release was completely abolished in both sites by the strial lesions, suggesting that the effect was mediated via a direct or indirect dopaminergic action on striatal output neurons. The grafts reinstated methamphetamine-induced stimulation of GABA release in striatal output targets to a level (as a proportion of baseline) that was similar to that seen in the control rats. The results support the view that activation of the dopaminergic inputs to the striatum is functionally excitatory on the major striatal output projections to the globus pallidus and substantia nigra pars reticulata. The results also support the hypothesis that striatal grafts have the capacity to become functionally incorporated by reciprocal graft-host connections into the neural circuitry of the host brain.