Jaw S P, Vuong Q T, Nguyen M
Department of Neurology, University of California Irvine 92717, USA.
Brain Res Bull. 1996;40(3):163-6. doi: 10.1016/0361-9230(96)00053-6.
Male Sprague-Dawley rats developed posthypoxic myoclonus following 10-min cardiac arrest and resuscitation. In current studies, roles of N-methyl-D-aspartate (NMDA), non-NMDA (a-amino-3-hydroxy-5-methylisoxazole-4-propionate, AMPA, and kainate), and metabotropic glutamate receptors in the pathophysiology of posthypoxic myoclonus were investigated. Treatments with the competitive or noncompetitive NMDA receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid (D[-]-AP-5) (ED50: 12.5 mg/kg, i.p.) or MK-801 maleate (ED50: 0.034 mg/kg, i.p.), and competitive or noncompetitive non-NMDA (AMPA/kainate) receptor antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX) (ED50: 9.25 nM/5 microliters, i.c.v.) or 1-(4-ami -nophenyl)-4-methyl-7,8-methylenedioxy -5H-2,3-benzodiazepine hydrochloride (GYKI 52466) (ED50: 0.67 mg/kg, IP), significantly decreased myoclonus episodes in rats. On the other hand, treatment with the metabotropic glutamate receptor antagonist, L(+)-2-amino-3-phosphonopropionic acid (L[+]-AP-3) (50 or 500 nM/5 microliters, i.c.v., exerted no significant effect on myoclonus scores in posthypoxic rats. These results indicate that activation of NMDA and non-NMDA receptors receptors may mediate posthypoxic myoclonus in rats, whereas, involvement of metabotropic glutamate receptors needs to be studied further.
雄性Sprague-Dawley大鼠在经历10分钟心脏骤停及复苏后出现了缺氧后肌阵挛。在当前研究中,对N-甲基-D-天冬氨酸(NMDA)、非NMDA(α-氨基-3-羟基-5-甲基异恶唑-4-丙酸,AMPA和海人藻酸)以及代谢型谷氨酸受体在缺氧后肌阵挛病理生理学中的作用进行了研究。用竞争性或非竞争性NMDA受体拮抗剂D-(-)-2-氨基-5-磷酸戊酸(D-(-)-AP-5)(半数有效剂量:12.5毫克/千克,腹腔注射)或马来酸氯胺酮(半数有效剂量:0.034毫克/千克,腹腔注射),以及竞争性或非竞争性非NMDA(AMPA/海人藻酸)受体拮抗剂6,7-二硝基喹喔啉-2,3-二酮(DNQX)(半数有效剂量:9.25纳摩尔/5微升,脑室内注射)或1-(4-氨基苯基)-4-甲基-7,8-亚甲基二氧基-5H-2,3-苯并二氮杂卓盐酸盐(GYKI 52466)(半数有效剂量:0.67毫克/千克,腹腔注射)进行治疗,可显著减少大鼠的肌阵挛发作次数。另一方面,用代谢型谷氨酸受体拮抗剂L-(+)-2-氨基-3-磷酸丙酸(L-(+)-AP-3)(50或500纳摩尔/5微升,脑室内注射)对缺氧后大鼠进行治疗,对肌阵挛评分没有显著影响。这些结果表明,NMDA和非NMDA受体的激活可能介导大鼠缺氧后肌阵挛,而代谢型谷氨酸受体的参与情况有待进一步研究。