Normalization of glutamate decarboxylase gene expression in the entopeduncular nucleus of rats with a unilateral 6-hydroxydopamine lesion correlates with increased GABAergic input following intermittent but not continuous levodopa.

摘要: Abstract The expression of mRNA encoding for the 67 kilodalton isoform glutamate decarboxylase (GAD67) was examined by in situ hybridization histochemistry entopeduncular nucleus (EP) adult rats with a 6-hydroxydopamine unilaterally lesion dopamine neurons. Our results provide original evidence that continuous or intermittent levodopa administration is equally effective at reversing lesion-induced increase GAD67 EP when compared vehicle controls. To characterize GABAergic interactions may mediate levodopa-induced alterations EP, double-labeling conducted combination radioactive and preproenkephalin preprotachykinin digoxigenin-labeled complementary RNA probes striatum. Levels labeling were significantly increased intermittent, but not levodopa. Analysis cellular level dorsal sector striatum revealed levels predominantly preproenkephalin-unlabeled neuronal profiles, presumably striatal/EP neurons (+99.3%). Saturation analyses 3 H-flunitrazepam binding to GABA A receptors showed paralleled significant decrease number (Bmax) ipsilateral lesion. Continuous failed alter striatal levels, affinity vehicle-treated These suggest normalization GAD gene involves an inhibition striatonigral/EP direct pathway. Conversely, effects on do appear be mediated GABA.