Intrathalamic Implants of GABA-Releasing Polymer Matrices Reduce Motor Impairments in Rats with Excitotoxically Lesioned Striata

Abstract Current models of basal ganglia disorders suggest that the choreoathetosis is the end result of reduced GABAergic inhibition of the motor thalamus. GABA-releasing polymer matrices or control matrices without GABA were implanted either unilaterally or bilaterally in the vicinity of the ventromedial thalamic nucleus of normal rats and of rats with unilateral or bilateral excitotoxic striatal lesions (rat model of Huntington's disease), to study the effects of these GABA-releasing matrices on amphetamine-induced rotational behavior (unilateral implants in unilaterally lesioned rats) and on overnight spontaneous locomotor activity (bilateral implants in bilaterally lesioned rats). Unilateral implants led to a reduction (about 25%) in motor asymmetry; the response was transitory, probably because of the exhaustion of GABA release by the matrix. Some rats showed a more marked and permanent reduction of motor asymmetry, but this was probably due to lesion of the ventromedial nucleus or its thalamocortical projection. Bilateral implants of GABA-releasing matrices (but not control matrices) led to a marked (about 65%) but again transitory reduction in the locomotor hyperactivity induced by bilateral striatal lesion. These results suggest that implantation of a GABA-releasing source may be an effective alternative to intrathalamic fetal-tissue grafts or lesions as an experimental approach to the treatment of hyperkinetic movement disorders.