Mansour A, Valenstein E S
Exp Neurol. 1985 Oct;90(1):224-37. doi: 10.1016/0014-4886(85)90055-x.
After a series of seven electroconvulsive shocks, mice (C57BL/6J) showed a marked change in their response to opiates. Although very large doses of mu agonists induce convulsions in normal control mice, our evidence indicated that this was accomplished through nonopiate mechanisms: they could not be blocked by naltrexone and the pattern of drug potencies (codeine greater than morphine greater than levorphanol) was not consistent with an opiate response. In contrast, after electroconvulsive shock small doses of mu agonists induced convulsions that could be blocked by naltrexone and the pattern of drug potency (levorphanol greater than morphine greater than codeine) was consistent with an opiate mechanism. Kappa drugs, on the other hand, produced convulsions in both control and ECS animals, although there was an enhanced responsiveness in the latter. Furthermore, the convulsions produced by kappa drugs were blocked by naltrexone and showed stereoselectivity in both control and ECS animals. The changes in responsiveness to mu and kappa opiates cannot be explained on the basis of a general increase in seizure susceptibility, as sensitivity to the nonopiate convulsant, strychnine, was not enhanced after electroconvulsive shock. The results point to a qualitative change in response to mu agonists after electroconvulsive shock, but only a change in sensitivity to kappa agonists.
在接受一系列七次电惊厥休克后，小鼠（C57BL/6J）对阿片类药物的反应出现了显著变化。虽然非常大剂量的μ激动剂会在正常对照小鼠中诱发惊厥，但我们的证据表明，这是通过非阿片类机制实现的：它们不能被纳曲酮阻断，并且药物效价模式（可待因大于吗啡大于左啡诺）与阿片类反应不一致。相比之下，在电惊厥休克后，小剂量的μ激动剂诱发的惊厥可被纳曲酮阻断，且药物效价模式（左啡诺大于吗啡大于可待因）与阿片类机制一致。另一方面，κ药物在对照动物和接受电惊厥休克的动物中均会引发惊厥，尽管后者的反应性有所增强。此外，κ药物引发的惊厥可被纳曲酮阻断，并且在对照动物和接受电惊厥休克的动物中均表现出立体选择性。对μ和κ阿片类药物反应性的变化不能基于癫痫易感性的普遍增加来解释，因为对非阿片类惊厥剂士的宁的敏感性在电惊厥休克后并未增强。结果表明，电惊厥休克后对μ激动剂的反应发生了质的变化，但仅对κ激动剂的敏感性发生了变化。
