THE ANTISEIZURE EFFICACIES OF MK-801, PHENCYCLIDINE, KETAMINE, AND MEMANTINE ARE ALTERED SELECTIVELY BY STRESS

Adaptive changes in the NMDA receptor complex occur in response to exp osure to stress. We have previously shown that the ability of MK-801, an uncompetitive NMDA receptor antagonist, to antagonize electrically precipitated tonic hindlimb extension is reduced 24 h after mice are f orced to swim for up to 10 min in cold water. The stress-induced reduc tion of the antiseizure efficacy of MK-801 stimulated the proposal tha t mice exposed to swim stress may serve as ''an intact animal model'' of altered or diminished NMDA-mediated neural transmission. In the cur rent investigation, the dose-dependent abilities for the antagonism of electrically precipitated seizures in mice were determined for MK-801 , phencyclidine, ketamine, and memantine. Interestingly, a single sess ion of cold water swim stress reduced the antiseizure efficacies of MK -801 and memantine without affecting phencyclidine and ketamine when t ested 24 h later. The data do not suggest that stress results in a sim ple reduction in the number of activated or open channels, but rather alters their size or charge characteristics. (C) 1997 Elsevier Science Inc.