Effects of oral administration of the competitive N-methyl-D-aspartate antagonist, CGP 40116, on passive avoidance,...

The effects were investigated of the potent competitive N-methyl-D-aspartate (NMDA) receptor antagonist CGP 40116[D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] on the performance of mice in water maze and passive avoidance tasks, and in wire suspension, rotarod, and cage activity tests. The drug was administered per os (p.o.) in its anticonvulsant dose range. CGP 40116 dose-dependently impaired passive avoidance learning when given before, but not when given after training. The antagonist (5, 10, and 20 mg/kg, administered 4 h before each training session) dose-dependently affected water maze acquisition, and impaired retention test performance in both hidden- and visible-platform water maze tasks. In addition, the drug dose-dependently decreased swimming speed during water maze acquisition. Repeated administration of CGP 40116 (20 mg/kg, p.o.) persistently decreased cage activity and wire suspension test performance, whereas motor coordination and equilibrium on the rotarod apparatus remained unimpaired. In our administration protocol, no tolerance was found to the effects of the drug on passive avoidance learning and neuromotor abilities. The parallel effects of CGP 40116 on memory and motor performance are discussed, and it was concluded that the antagonist impairs neuromotor abilities and also induces memory impairments which cannot be entirely reduced to motor interference.