Mansour A, Valenstein E S
Exp Neurol. 1986 Jun;92(3):571-82. doi: 10.1016/0014-4886(86)90299-2.
Morphine, a mu-opiate agonist, and ethylketazocine, a kappa-opiate agonist, produce distinct behavioral, pharmacologic, and biochemical effects. In the mouse, large doses of morphine produce convulsions that are usually lethal and that cannot be blocked by naltrexone, whereas ethylketazocine produces nonlethal clonic convulsions that can be blocked by naltrexone. Moreover, mice made tolerant to morphine failed to show cross-tolerance to ethylketazocine, suggesting that the convulsions induced by these drugs are not mediated via a common opioid mechanism. Following a series of electroconvulsive shocks, both morphine and ethylketazocine produced clonic convulsions that were not lethal and that could be blocked by naltrexone. Furthermore, electroconvulsive shock-treated animals made tolerant to morphine-induced convulsions showed cross-tolerance to ethylketazocine. These data suggest that electroconvulsive shock may alter kappa-opioid systems in such a way as to allow mu-agonists to be functional at these sites.
吗啡是一种μ阿片受体激动剂，而乙基酮唑辛是一种κ阿片受体激动剂，它们会产生不同的行为、药理和生化效应。在小鼠中，大剂量吗啡会引发惊厥，通常是致命的，且不能被纳曲酮阻断，而乙基酮唑辛会引发非致命性阵挛性惊厥，可被纳曲酮阻断。此外，对吗啡产生耐受性的小鼠对乙基酮唑辛未表现出交叉耐受性，这表明这些药物引发的惊厥并非通过共同的阿片类机制介导。在接受一系列电休克治疗后，吗啡和乙基酮唑辛都会引发非致命性的阵挛性惊厥，且可被纳曲酮阻断。此外，经电休克治疗且对吗啡诱导的惊厥产生耐受性的动物对乙基酮唑辛表现出交叉耐受性。这些数据表明，电休克可能会改变κ阿片系统，使得μ激动剂在这些部位发挥作用。
