The effects of NMDA receptor antagonists at anticonvulsive doses on the performance of rats in the water maze task.

In the present study we investigated the effects of two competitive NMDA receptor antagonists, CGP 37849 (DL-(E)-2-amino-4-methyl-phosphono-3-pentonoic acid) and CGP 39551 (carboxyethyl ester of CGP 37849) as well as MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenz(a,d)cycloheptene-5,10-imine hydrogen maleate), a non-competitive antagonist, administered systemically before training, on the acquisition of a water maze task used to assess spatial learning and memory in rats. The competitive NMDA receptor antagonists dose dependently impaired water maze acquisition (increased escape distance), but did not significantly affect swimming speed in rats. MK-801 induced clear behavioral effects and impaired the acquisition of the water maze task. However, as training advanced drug-treated rats did show a decrease in distance swam per trial before encountering the platform in the water pool. This suggests that drug treatments did not abolish learning. When the anticonvulsive properties of the drugs were determined, MK-801 did not show any protection in the maximal electroshock (MES) test at doses already impairing the acquisition of the water maze task while the two competitive NMDA receptor antagonists protected the rats against seizures at doses not impairing acquisition. This result suggests a wider therapeutic range for CGP 39551 and especially for CGP 37849 than for MK-801 in the treatment of epilepsy.