CONSEQUENCE OF NIGROSTRIATAL DENERVATION AND L-DOPA THERAPY ON THE EXPRESSION OF GLUTAMIC-ACID DECARBOXYLASE MESSENGER-RNA IN THE PALLIDUM

To examine the consequences of nigrostriatal denervation and L-dopa tr eatment on the basal ganglia output system, we analyzed, by quantitati ve in situ hybridization, the messenger RNA coding for glutamic acid d ecarboxylase (M(r) 67,000) (GAD(67) mRNA) in pallidal cells from patie nts with Parkinson's disease (PD), monkeys rendered parkinsonian by 1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) receiving or not rec eiving L-dopa, and their respective control subjects. In MPTP-treated monkeys, the expression of GAD(67) mRNA was increased in cells from th e internal pallidum, and this effect was abolished by L-dopa treatment . There were no differences in the levels of GAD(67) mRNA between pati ents with PD, who were all treated with L-dopa, and control subjects. These results indicate that the level of GAD(67) mRNA is increased in the cells of the internal pallidum after nigrostriatal dopaminergic de nervation and that this increase can be reversed by L-dopa therapy.