NMDA antagonists potentiate scopolamine-induced amnesic effect

The effects of N-methyl-D-aspartate NMDA receptor antagonists on scopolamine-induced amnesia and on delay-interposed short-term memory performance were investigated using an 8-arm radial maze in rats. Scopolamine, a muscarinic antagonist, deteriorated the radial maze performance, while MK-801, an NMDA receptor channel blocker and CGS-19755, a competitive NMDA receptor antagonist, showed no obstruction to the spatial cognition in the non-delayed maze task. MK-801 (0.01-0.03 mg/kg, i.v.) and CGS-19755 (1-10 mg/kg, i.v.) significantly augmented scopolamine-induced deficit in the non-delayed maze task and impaired the short-term memory in the 5-min delay-interposed task. These results suggest that NMDA antagonists have a negative action on short-term memory and that the interaction between the NMDA and the central muscarinic system plays a role in modulating the cognitive function.