Striatal preproenkephalin gene expression is upregulated in acute but not chronic parkinsonian monkeys: Implications for the contribution of the indirect striatopallidal circuit to parkinsonian symptomatololgy

This study examined the extent of striatal dopamine (DA) denervation and co incident expression of preproenkephalin (PPE) mRNA in monkeys made parkinso nian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. Some animals (n = 4) became moderately parkinsonian after receiving large doses of MPTP over short periods of time and were symptomatic for only a sh ort period of time (1-3 months; acute parkinsonian group). Other animals be came moderately parkinsonian after receiving either escalating doses of MPT P over long periods (4-6 months; n = 5) or a high dose of MPTP over a short period (<1 month; n = 1) and remained symptomatic for an extended period ( >8 months; chronic parkinsonian group). Despite similar symptomatology and similar degrees of striatal DA denervation at the time of their deaths, onl y acute parkinsonian animals had significantly increased PPE expression in sensorimotor striatal regions. PPE expression in chronic parkinsonian anima ls was either not changed or significantly decreased in most striatal regio ns. These findings suggest that the duration and not the extent of striatal DA denervation is a critical factor in modulating changes in striatal PPE expression. Furthermore, these results question the role of increased activ ity in the enkephalin-containing indirect striatopallidal pathway in the ex pression of parkinsonian symptoms.