Search

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.

We examined possible genetic contributions to MK-801-elicited "popping" behavior in mice. MK-801-elicited "popping" behavior may represent a preclinical screening paradigm for identifying novel antipsychotic medications. Specifically, we studied the sensitivity of four inbred strains of mice (BALB/c, C57BL/6, AKR, and DBA/2) to MK-801-elicited "popping" behavior and compared their response to the outbred NIH Swiss strain in which the behavior was first characterized. The BALB/c strain was most sensitive to the elicitation of MK-801 induced popping behavior, whereas the other inbred strains were less sensitive than the outbred strain. The identification of strain differences in MK-801-elicited "popping" behavior suggests an important role for genetic factors in the elicitation of MK-801 "popping" behavior in mice.