INCREASED SUSCEPTIBILITY TO MPTP TOXICITY IN MIDDLE-AGED RHESUS-MONKEYS

In the present study, age-associated effects of the neurotoxin 1-methy l-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) administered via the righ t carotid artery were evaluated pre- and post-MPTP treatment in 26 fem ale rhesus monkeys ranging in age from young adulthood to middle age ( 5 to 23 years old). A significant inverse correlation was seen between age and MPTP dose needed to produce stable, moderate parkinsonian fea tures. Rhesus in the 5- to 9-year-old group required approximately thr ee times the amount of MPTP as 20- to 23-year-old animals. Even though they received less MPTP, the older animals consistently displayed mor e severe bradykinesia, upper limb rigidity, and balance and gait abnor malities. Prior to MPTP treatment, home cage activity levels were stro ngly age dependent, with animals in the 10- to 19-year and 20- to 23-y ear groups displaying significantly less daytime activity than 5- to 9 -year-old rhesus. Home cage activity levels tended to decrease in all age groups following MPTP treatment, but significant decreases were on ly measured in daytime activity in the 10- to 19 and 20- to 23-year ag e groups .