MPTP-Induced Parkinsonism in the Monkey: Neurochemical Pathology, Complications of Treatment and Pathophysiological Mechanisms

Abstract

ABSTRACT:MPTP induces parkinsonism in monkeys by destruction of the substantia nigra, pars compacta. It can also damage ventral tegmental dopamine neurones and the noradrenergic locus coeruleus, both of which may be affected in Parkinson's disease. Motor symptoms in MPTP-treated monkeys respond readily to levodopa or dopamine agonist therapy. Administration of levodopa over 4-8 weeks leads to the emergence of “peak- dose” dyskinesia. Such abnormal movements are not seen following challenge doses of levodopa in animals not on long-term therapy. Radioligand studies reveal a 40-180% increase in D2 receptor binding in the striatum of parkinsonian monkeys. 2-deoxyglucose studies of regional brain metabolism indicate that MPTP-induced parkinsonism is characterised by abnormally increased activity of medial pallidal neurones which project to the thalamus and pedunculopontine nucleus and reduced activity of subthalamic nucleus neurones.