Changes in the local cerebral metabolic rate for glucose in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate model of Parkinson's disease.

Nine adult monkeys (Macaca fascicularis) were used in this study. Five animals were used as controls. Three animals were injected intravenously daily with 0.5 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) over a 4-day period; one animal was injected weekly over a 4-week period. Neurological examination of the MPTP-treated animals revealed a flexed posture of trunk and extremities, bradykinesia, increased tone without cogwheel rigidity, loss of vestibular righting reflexes, decreased vocalization and swallowing, failure of upgaze and abnormal pursuit eye movements. Reflexes were hyperactive. The compound 2-deoxy-D-[14C]glucose (2-DG) was utilized for the determination of the local cerebral metabolic rate for glucose (lCMRg). A generalized decrease in lCMRg was noted in all cerebral cortical areas as compared to control values. The cerebellar cortex demonstrated no change in lCMRg. Areas that demonstrated a significant increase in lCMRg were: the internal and external segments of the globus pallidus (P less than 0.01), the pars compacta and the pars reticulata of the substantia nigra (P less than 0.05). Areas that demonstrated a significant decrease in lCMRg were: the head of the caudate nucleus (P less than 0.05), the anterior dorsomedial putamen (P less than 0.05) and the anterior segment of the subthalamic nucleus (P less than 0.05). The 2-DG analysis of the MPTP primate model of Parkinson's disease is particularly suited to demonstrate areas in the central nervous system that are affected by this neurotoxin. Further studies of these areas may lead to a better understanding of the mechanisms that underlie the clinical symptomatology of Parkinson's disease.