Abstract
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 microgram/kg) significantly improved the performance on this task. High-dose D-cycloserine (8000 microgram/kg) or MK-801 (10-32 microgram/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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cognition / drug effects*
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Cycloserine / pharmacology
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Cycloserine / therapeutic use*
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Cycloserine / toxicity
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Discrimination, Psychological / drug effects
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Disease Models, Animal
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Dizocilpine Maleate / pharmacology
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Amino Acid Antagonists / therapeutic use
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Excitatory Amino Acid Antagonists / toxicity
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Glycine / agonists*
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Glycine / antagonists & inhibitors
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MPTP Poisoning / drug therapy*
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MPTP Poisoning / psychology
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Macaca fascicularis
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Male
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Neuroprotective Agents / pharmacology
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Neuroprotective Agents / therapeutic use*
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Neuroprotective Agents / toxicity
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Parkinson Disease, Secondary / chemically induced
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Parkinson Disease, Secondary / drug therapy*
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Psychomotor Performance / drug effects*
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Reaction Time / drug effects
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Visual Perception / drug effects
Substances
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Excitatory Amino Acid Antagonists
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Neuroprotective Agents
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Dizocilpine Maleate
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Cycloserine
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Glycine