Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, VA 23507–1912, USA.
Epilepsy Behav. 2011 Aug;21(4):352-5. doi: 10.1016/j.yebeh.2011.03.026. Epub 2011 Jun 16.
The ability of MK-801 (dizocilpine), a noncompetitive N-methyl D-aspartate (NMDA) antagonist, to antagonize electrical seizures is reduced in stressed mice. Stress-associated alterations in seizure susceptibility and diminished efficacy of antiseizure medications in humans have been reported [Joëls, 2009; Haut et al., 2007; Moshe et al., 2008]; thus, these experimental observations implicate altered endogenous tone of NMDA receptor-mediated neurotransmission in clinically adverse effects of stress on seizure proneness and treatment. The current exploratory experiment examined the effect of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), an antagonist of mGluR5, administered prior to stress on the stress-induced reduction of MK-801's antiseizure effect in Swiss-Webster and Balb/c mice; the Balb/c mouse is behaviorally hypersensitive to MK-801. Interestingly, the data suggest that MPEP can attenuate the severity of the stress-induced reduction of MK-801's antiseizure effect in the Balb/c strain. Thus, mGluR5 could serve as a target for strategies for adjuvant treatment of seizures exacerbated by stress.
MK-801（地卓西平）是一种非竞争性 N-甲基-D-天冬氨酸（NMDA）拮抗剂，其拮抗电惊厥的能力在应激小鼠中降低。已有报道称，应激相关的癫痫易感性改变和抗癫痫药物疗效降低与人类有关[Joëls，2009；Haut 等人，2007；Moshe 等人，2008]；因此，这些实验观察表明 NMDA 受体介导的神经传递的内源性张力改变与应激对癫痫易感性和治疗的临床不良影响有关。目前的探索性实验研究了 2-甲基-6-（苯乙炔基）-吡啶（MPEP），一种 mGluR5 拮抗剂，在应激前给药对瑞士-韦伯斯特和 Balb/c 小鼠中 MK-801 抗惊厥作用的应激诱导降低的影响；Balb/c 小鼠对 MK-801 的行为敏感。有趣的是，数据表明 MPEP 可以减轻 Balb/c 品系中应激诱导的 MK-801 抗惊厥作用降低的严重程度。因此，mGluR5 可以作为应激加重癫痫发作的辅助治疗策略的靶点。
