Khanna J M, Morato G S, Shah G, Chau A, Kalant H
Department of Pharmacology, University of Toronto, Canada.
Brain Res Bull. 1993;32(1):43-7. doi: 10.1016/0361-9230(93)90317-5.
To examine whether nitric oxide was involved in the development of rapid tolerance to the motor-incoordinating effects of ethanol (tilt-plane test), three experiments were undertaken in a rapid tolerance paradigm in rats. The first experiment tested the effect of the nitric oxide synthase inhibitor, L-nitro-arginine, on the acquisition of ethanol tolerance. The second compared the effects of L-nitro-arginine with those of its inactive isomer, D-nitro-arginine. The third examined whether overload with the substrate L-arginine would prevent the action of L-nitro-arginine on rapid tolerance. The results demonstrated that L-nitro-arginine prevented the development of rapid tolerance, while D-nitro-arginine was ineffective. An excess of the substrate L-arginine reversed the inhibitory action of L-nitro-arginine on tolerance development. These data suggest that nitric oxide may play a role in the development of tolerance to ethanol. The role of nitric oxide in ethanol tolerance may be similar to its role in memory and learning, involving facilitation of transmission in certain NMDA synapses.
为研究一氧化氮是否参与了对乙醇运动协调效应快速耐受性的形成（倾斜平面试验），在大鼠快速耐受性范式下进行了三项实验。第一项实验测试一氧化氮合酶抑制剂L-硝基精氨酸对乙醇耐受性获得的影响。第二项实验比较了L-硝基精氨酸与其无活性异构体D-硝基精氨酸的作用。第三项实验研究底物L-精氨酸过量是否会阻止L-硝基精氨酸对快速耐受性的作用。结果表明，L-硝基精氨酸可阻止快速耐受性的形成，而D-硝基精氨酸则无效。过量的底物L-精氨酸可逆转L-硝基精氨酸对耐受性形成的抑制作用。这些数据表明一氧化氮可能在乙醇耐受性形成中起作用。一氧化氮在乙醇耐受性中的作用可能与其在记忆和学习中的作用相似，涉及促进某些N-甲基-D-天冬氨酸（NMDA）突触的传递。
