Itzhak Y
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, FL 33101, USA.
Mol Neurobiol. 1995 Aug-Dec;11(1-3):217-22. doi: 10.1007/BF02740696.
Previous studies proposed the involvement of the N-methyl-D-aspartate (NMDA) type of glutamate receptors in the development of sensitization to the convulsive effect of cocaine (cocaine kindling). The present study was undertaken to determine, first, if cocaine kindling is associated with enhanced sensitivity of the NMDA receptor to the convulsive response of N-methyl-D,L-aspartate (NMDLA), and second, whether in vivo modulation of nitric oxide synthase (NOS) function regulates the development of cocaine kindling. The following results were observed: 1. Cocaine-kindled animals were significantly more susceptible to the convulsive effect of the NMDA receptor agonist NMDLA than saline controls; 2. Pretreatment with the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg; ip) blocked the development of cocaine kindling; 3. The protective effect of L-NAME was partially reversed with the coadministration of the NOS substrate, L-arginine (300 mg/kg; ip), but not D-arginine; and 4. L-Arginine (300 mg/kg; ip), but not D-arginine, amplified the development of cocaine kindling. Taken together, these findings suggest that supersensitivity of the NMDA receptor and activation of NOS may underlie the development of cocaine kindling.
先前的研究表明，N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体参与了对可卡因惊厥作用（可卡因点燃）的致敏过程。本研究旨在首先确定可卡因点燃是否与NMDA受体对N-甲基-D,L-天冬氨酸（NMDLA）惊厥反应的敏感性增强有关，其次确定一氧化氮合酶（NOS）功能的体内调节是否调节可卡因点燃的发展。观察到以下结果：1. 可卡因点燃的动物比生理盐水对照组对NMDA受体激动剂NMDLA的惊厥作用明显更敏感；2. 用NOS抑制剂NG-硝基-L-精氨酸甲酯（L-NAME；100 mg/kg；腹腔注射）预处理可阻断可卡因点燃的发展；3. 同时给予NOS底物L-精氨酸（300 mg/kg；腹腔注射）可部分逆转L-NAME的保护作用，而D-精氨酸则不能；4. L-精氨酸（300 mg/kg；腹腔注射）可增强可卡因点燃的发展，而D-精氨酸则不能。综上所述，这些发现表明NMDA受体的超敏反应和NOS的激活可能是可卡因点燃发展的基础。
