Schneider, JS; Tinker, JP; Van Velson, M; Menzaghi, F; Lloyd, GK
Nicotinic Acetylcholine Receptor Agonist SIB-1508Y Improves Cognitive Functioning in Chronic Low-Dose MPTP-Treated Monkeys
Teil von
  • The Journal of pharmacology and experimental therapeutics, 1999-08-01, Vol.290 (2), p.731-739
Ort / Verlag
BETHESDA: American Society for Pharmacology and Experimental Therapeutics
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Web of Science
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 Parkinson’s disease.

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