NMDA receptors in mice bred to be prone or resistant to ethanol withdrawal seizures

Selective breeding has produced replicate lines of mice that are prone (WSP) or resistant (WSR) to ethanol withdrawal seizures. Ethanol-naive WSP mice inherently have a greater number of hippocampal binding sites for the NMDA receptor-gated ion channel blocker, MK-801, than ethanol-naive WSR mice. After chronic ethanol ingestion, hippocampal (but not cerebral cortical) MK-801 binding sites increase in both lines of mice. However, the number of MK-801 binding sites in the ethanol-treated WSR mice does not exceed the number of MK-801 binding sites in untreated WSP mice. At the time of ethanol withdrawal, the number of hippocampal MK-801 binding sites in each line of WSP mice is 50-70% higher than the number of such sites in WSR mice. Given the past evidence for a role of the NMDA receptor in seizures, the results implicate hippocampal NMDA receptor-gated channels in the generation of ethanol withdrawal seizures.