Chronic exposure to low doses of MPTP. I. Cognitive deficits in motor asymptomatic monkeys.

Cognitive deficits which may occur following chronic low-dose exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied in monkeys who remained motor asymptomatic for parkinsonism throughout the study. The tasks used to assess cognitive functioning are those which have proved in the past to be sensitive to disruption of frontal cortical and or striatal integrity (delayed response and delayed alternation) or sensitive to inferior temporal lobe dysfunction (visual pattern discrimination). Since Parkinson's disease patients have been described as exhibiting frontal signs, we were interested to examine whether MPTP-treated monkeys might exhibit deficits on frontally-mediated tasks, without the confound of motor disturbances. We found that macaque nemistrina monkeys exposed to cumulative doses of 14.94-75.42 mg of MPTP over periods ranging from 5 to 13 months never developed parkinsonian motor signs. However, all 4 animals examined showed significant post-MPTP deficits in delayed response and delayed alternation performance, while visual pattern discrimination performance remained intact. These animals also developed other behavioral problems including irritability and decreased attentiveness. These results show that MPTP can cause specific cognitive deficits independent of the motor deficits which can be produced by this toxin.