Inbred mouse strains differ in their sensitivity to an antiseizure effect of MK-801

The ability of MK-801 to antagonize the electrical precipitation of tonic hindlimb extension was studied in four inbred mouse strains (BALB/c, C57BL/6, AKR, and DBA/2) and the outbred NM Swiss strain, using an incremental electroconvulsive shock (IECS) procedure. Strains differed in the threshold voltages required for the electrical precipitation of tonic hindlimb extension. They also differed in their sensitivity to antagonism of electrically precipitated tonic hindlimb extension by MK-801. The BALB/c, C57BL, and DBA strains required a significant elevation of the threshold voltage for the elicitation of tonic hindlimb extension in response to 0.18 mg/kg of MK-801, the lowest dose tested; whereas the AKR and NIH Swiss strains did not respond to this dose with an increase of threshold voltage for the elicitation of tonic hindlimb extension. Moreover, a higher percentage of BALB/c mice were maximally protected against seizure elicitation by MK-801 over a dosage range of 0.18 to 0.56 mg/kg, compared to the other strains. The demonstration of strain differences suggests that genetic factors influence the anticonvulsant properties of MK-801.