Parallel increases in striatal glutamic acid decarboxylase activity and mRNA levels in rats with lesions of the nigrostriatal pathway.

Adult male rats were lesioned with 6-hydroxydopamine in order to destroy the nigrostriatal dopaminergic projections. In rats with such a lesion, we found a parallel increase in glutamic acid decarboxylase (GAD) activity and GAD mRNA in the striatum ipsilateral to the lesion at 4 weeks and 4 months after the lesion. These observations support the proposal that nigral dopaminergic neurons exert a tonic inhibitory control over the striatal GABAergic neurons. Our observations also suggest that the dopaminergic neurons can inhibit gene expression in striatal GABAergic neurons and that the enhanced striatal GAD activity following lesions of the dopaminergic projections is due to 'de novo' synthesis of the enzyme.