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 exposure to stress. We have previously shown that the ability of MK-801, an uncompetitive NMDA receptor antagonist, to antagonize electrically precipitated tonic hind-limb extension is reduced 24 h after mice are forced to swim for up to 10 min in cold water. The stress-induced reduction of the antiseizure efficacy of MK-801 stimulated the proposal that mice exposed to swim stress may serve as "an intact animal model" of altered or diminished NMDA-mediated neural transmission. In the current 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 session of cold water swim stress reduced the antiseizure efficacies of MK-801 and memantine without affecting phencyclidine and ketamine when tested 24 h later. The data do not suggest that stress results in a simple reduction in the number of activated or open channels, but rather alters their size or charge characteristics.
Deutsch
S I
SI
Psychiatry Service, Department of Veterans Affairs Medical Center, Washington, DC 20422, USA.
Mastropaolo
J
J
Riggs
R L
RL
Rosse
R B
RB
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003080:Cold Temperature; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D008559:Memantine / Q000494:pharmacology; D051379:Mice; D010622:Phencyclidine / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013315:Stress, Psychological / Q000503:physiopathology*
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D008559:Memantine