Monkeys that receive chronic low-dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration have difficulty performing
numerous cognitive tasks. This study further examines the extent to which chronic low-dose MPTP exposure affects performance
of a visual memory task [variable delayed response (VDR)] with both attentional and short-term memory components and assesses
the effects of the novel neuronal nicotinic acetylcholine receptor agonist SIB-1508Y and levodopa on cognitive task performance.
Before MPTP treatment, these monkeys displayed a delay-dependent decrement in performance on the VDR task and performed well
on delayed matching-to-sample and visual pattern discrimination tasks. Chronic low-dose MPTP treatment caused a shift to a
delay-independent pattern of responding on the VDR task, such that short-delay trials were performed as poorly as long-delay
trials. There were also deficits in performing the delayed matching-to-sample task, whereas visual discrimination performance
remained intact. SIB-1508Y normalized the pattern of response on the VDR task by significantly improving performance on short-delay
trials and on the delayed matching-to-sample task. These effects lasted up to 24 to 48 h after SIB-1508Y administration. Neither
levodopa nor nicotine significantly improved task performance. These results suggest that chronic low-dose MPTP exposure results
in a cognitive disturbance that can be corrected by the nicotinic acetylcholine receptor agonist SIB-1508Y but not by levodopa.
Thus, SIB-1508Y may be useful in the treatment of the cognitive deficits in Parkinsonâs disease.