Effects of the partial glycine agonist d-cycloserine on cognitive functioning in chronic low dose MPTP-treated monkeys

d-Cycloserine, a partial agonist at the glycine recognition site of the N-methyl- d-aspartate (NMDA) receptor complex, has been shown to facilitate certain forms of memory formation and to improve visual recognition memory in normal monkeys. In the present study, the effects of d-cycloserine on spatial short-term memory 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 the performance of a variable delayed-response task (VDR). Single administration of d-cycloserine (320 or 1000 μg/kg) significantly improved the performance on this task. High-dose d-cycloserine (8000 μg/kg) or MK-801 (10-32 μg/kg) administration had no effects on delayed-response performance but impaired performance on a visual discrimination (VD) task that was not adversely affected by MPTP administration. These results show that at low doses, d-cycloserine has cognition-enhancing properties in this model of early Parkinsonism.