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 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.
Schneider
J S
JS
Department of Pathology, Thomas Jefferson University, 1020 Locust Street, 521 JAH, Philadelphia, PA, USA. jay.schneider@mail.tju.edu
Tinker
J P
JP
Van Velson
M
M
Giardiniere
M
M
D000818:Animals; D003071:Cognition / Q000187:drug effects*; D003523:Cycloserine / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D004192:Discrimination, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D005998:Glycine / Q000819:agonists* / Q000037:antagonists & inhibitors; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000523:psychology; D008252:Macaca fascicularis; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D011597:Psychomotor Performance / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D014796:Visual Perception / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016291:Dizocilpine Maleate; D003523:Cycloserine; D005998:Glycine