Valverius P, Crabbe J C, Hoffman P L, Tabakoff B
Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892.
Eur J Pharmacol. 1990 Aug 2;184(1):185-9. doi: 10.1016/0014-2999(90)90681-u.
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.
选择性育种培育出了对乙醇戒断性癫痫发作易感（WSP）或有抗性（WSR）的小鼠品系。未接触过乙醇的WSP小鼠，其海马中N-甲基-D-天冬氨酸（NMDA）受体门控离子通道阻滞剂MK-801的结合位点数量，天生就比未接触过乙醇的WSR小鼠更多。长期摄入乙醇后，这两种品系小鼠的海马（而非大脑皮质）中MK-801结合位点均会增加。然而，经乙醇处理的WSR小鼠中MK-801结合位点的数量并未超过未处理的WSP小鼠中MK-801结合位点的数量。在乙醇戒断时，各品系WSP小鼠海马中MK-801结合位点的数量比WSR小鼠中此类位点的数量高50%-70%。鉴于过去有证据表明NMDA受体在癫痫发作中起作用，这些结果表明海马NMDA受体门控通道参与了乙醇戒断性癫痫发作的产生。
