Extrastriatal dopamine in symptomatic and asymptomatic rhesus monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

Abstract

We analyzed in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus monkeys, with and without parkinsonian symptoms, the regional changes in dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and tyrosine hydroxylase activity (TH). Symptomatic monkeys had wide-spread DA loss in subcortical and cortical regions. However, the magnitude of this MPTP-induced DA reduction was markedly smaller than the DA loss in the caudate nucleus and putamen, where only less than 1% DA remained. No comparable loss of DA was found in the subcortical extrastriatal regions of asymptomatic MPTP monkeys, despite more than 90% DA loss in the striatal nuclei. The most pronounced difference in DA levels between the symptomatic and the asymptomatic group was observed in nucleus accumbens, nucleus of the stria terminalis, ventral tegmental area, globus pallidus and the cingulate gyrus. Levels of DOPAC and TH activity paralleled the behavior of DA. In contrast, the concentration of HVA was reduced in many brain regions of both symptomatic and asymptomatic monkeys. These effects of MPTP on extrastriatal DA levels in the rhesus monkey are compared with DA and HVA changes in the brain of patients with Parkinson's disease, and their possible contributory role for the production, by MPTP, of a permanent parkinsonian condition is discussed.