MPTP-Induced pallidal lesions in rhesus monkeys

Dopamine neurons in the substantia nigra of the midbrain are the primary neuronal population affected by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) toxicity, which produces the pathological and behavioral features of Parkinson's disease in nonhuman primates and man. We have identified another injury site in magnetic resonance imaging (MRI) brain scans in 13 of 37 rhesus monkeys taken 10-12 months after administration of this neurotoxin via the right carotid artery. Focal lesions, ranging in volume from 6.75 to 60 mm3 in the rostral globus pallidus region, were seen on the right side of the brain in these 13 animals in addition to the midbrain effects. While no significant differences were seen between globus pallidus lesioned and nonlesioned animals in the severity of MPTP-induced parkinsonian symptoms, the response to levodopa was muted in pallidal-lesioned animals. To confirm the role of neurotoxicity in producing the lesions, brain scans from an additional 12 monkeys were evaluated during the acute period following exposure to either MPTP (n = 6) or saline (n = 6). Focal lesions in the rostral globus pallidus were seen as early as 2-4 h following a carotid artery infusion in two of six MPTP recipients, but no evidence of injury was seen in saline recipients. The globus pallidus includes important components of the neural circuitry regulating motor functions. The present results indicate that in addition to midbrain dopamine neurons, a focal region of the rostral globus pallidus is selectively vulnerable to MPTP toxicity.