Abstract
A number of neuropeptides are affected in Parkinson's disease and the enzyme proline endopeptidase contributes to the degradation of many of these neuropeptides, some of which are linked to a variety of cognitive functions. In the present study, the effects of the highly potent proline endopeptidase inhibitor S 17092 on cognitive deficits in monkeys induced by chronic low dose 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration were examined. Chronic low dose MPTP administration resulted in deficits in performance of variable delayed response, delayed matching-to-sample, and delayed alternation tasks. Seven day oral administration of S 17092 followed by single dose administration of the same dose on the day of testing significantly improved overall performance on these tasks. The most effective dose of S 17092 was 3 mg/kg. These results indicate that S 17092 has cognition-enhancing properties in this model of early parkinsonism.
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Acknowledgements
This research was supported by the Institut de Recherches Internationales Servier. Dr. Schneider has been a paid consultant of the Institut de Recherches Internationales Servier and does not currently have a financial or other involvement with this organization. Dr. Morain is an employee of the Institut de Recherches Internationales Servier.
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Schneider, J., Giardiniere, M. & Morain, P. Effects of the Prolyl Endopeptidase Inhibitor S 17092 on Cognitive Deficits in Chronic Low Dose MPTP-Treated Monkeys. Neuropsychopharmacol 26, 176–182 (2002). https://doi.org/10.1016/S0893-133X(01)00307-4
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DOI: https://doi.org/10.1016/S0893-133X(01)00307-4
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