Deutsch S I, Mastropaolo J, Riggs R L, Rosse R B
Psychiatry Service, Department of Veterans Affairs Medical Center, Washington, DC 20422, USA.
Pharmacol Biochem Behav. 1997 Nov;58(3):709-12. doi: 10.1016/s0091-3057(97)90014-9.
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.
NMDA受体复合物会发生适应性变化以响应应激暴露。我们之前已经表明，非竞争性NMDA受体拮抗剂MK-801拮抗电诱发的强直性后肢伸展的能力，在小鼠被迫在冷水中游泳长达10分钟后24小时会降低。应激诱导的MK-801抗癫痫疗效降低促使人们提出，暴露于游泳应激的小鼠可能作为NMDA介导的神经传递改变或减弱的“完整动物模型”。在当前研究中，测定了MK-801、苯环己哌啶、氯胺酮和美金刚对小鼠电诱发癫痫的剂量依赖性拮抗能力。有趣的是，单次冷水游泳应激在24小时后测试时，降低了MK-801和美金刚的抗癫痫疗效，而不影响苯环己哌啶和氯胺酮。这些数据并不表明应激会导致活化或开放通道数量简单减少，而是改变了它们的大小或电荷特性。
