The effects of d-cycloserine, a partial agonist at the glycine binding site, on spatial learning and working memory in scopolamine-treated rats.
The present study investigated the effect of d-cycloserine, a partial agonist at the glycine binding site on NMDA receptor complex, on the performance of scopolamine-treated adult rats in a water maze task assessing spatial learning and in a delayed non-matching to position task assessing working memory in a spatial context. In the spatial learning task, scopolamine (0.4 mg/kg, i.p.) impaired acquisition (increased escape latency and distance) and increased swimming speed of rats. D-cycloserine (1.0 mg/kg, i.p.) reversed the deficits in acquisition performance but not the increases in behavioral activity. In the working memory task, scopolamine (0.2 mg/kg, i.p.) produced deficits on nonmnemonic rather than on mnemonic performance factors; scopolamine delay-independently decreased the percent correct responses and reduced behavioral activity of rats. D-cycloserine (1.0, 3.0 and 10 mg/kg, i.p.) did not reverse these performance deficits. When administered alone, the moderate to higher doses of d-cycloserine had no effects on working memory but the lower dose produced slight deficits in mnemonic performance factors; the 1.0 mg/kg dose delay-dependently decreased the percent correct responses without affecting behavioral activity of rats. In the water maze task, d-cycloserine had no effects on acquisition performance or behavioral activity of rats. These results suggest that acute, systemic administration of d-cycloserine does not improve spatial learning or working memory. However, at appropriate doses this agent may be efficacious in disease states of central cholinergic hypofunction since 1.0 mg/kg d-cycloserine was able to reverse the scopolamine-induced deficits in acquisition.
Department of Neurology, University of Kuopio, Finland.
M
M
Pitkänen
J
J
Sirviö
E
E
MacDonald
T
T
Ekonsalo
P
P
Riekkinen
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D003523:Cycloserine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018684:Glycine Agents / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018009:Receptors, Glycine / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D012055:Reinforcement Schedule; D012601:Scopolamine / Q000494:pharmacology
D000963:Antimetabolites; D018684:Glycine Agents; D018727:Muscarinic Antagonists; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D003523:Cycloserine; D012601:Scopolamine