Urca G, Harouni A, Sarne Y
Eur J Pharmacol. 1982 Jul 9;81(2):237-43. doi: 10.1016/0014-2999(82)90441-1.
Acute administration of electroconvulsive shock (ECS) has been shown previously to produce potent analgesia which is only partially reversed by naloxone but shows almost complete tolerance after both repeated ECS and chronic morphine administration. In an attempt to elucidate the underlying basis of ECS analgesia it was recently compared with the analgesic effect of a newly identified opioid, humoral (H)-endorphin. Intracerebroventricular (i.c.v.) injection of H-endorphin to rats produces a dose-related analgesic effect as measured by the tail flick method. Furthermore, 4 days of daily i.c.v. injections of 40 microgram of morphine resulted in complete tolerance to the analgesic effect of H-endorphin. However, naloxone only caused a partial reversal of H-endorphin analgesia. Surprisingly only the lower dose of 1 mg/kg exerted a significant antagonistic effect while a higher dose of 10 mg/kg of the antagonist was without effect. A similar unconventional profile of the effect of naloxone could be seen with ECS analgesia. Here, pretreatment with 1 mg/kg of naloxone significantly attenuated analgesia, whereas administration of 10 mg/kg of the antagonist was without effect. In contrast, catalepsy measured in the same animals was not affected by 1 mg/kg of naloxone but increasing the dose to 10 mg/kg produced a significant attenuation of ECS catalepsy. The opioid nature of H-endorphin analgesia on one hand and the unconventional dose relation with naloxone of both H-endorphin and ECS analgesia on the other hand, suggests the involvement of this opioid in analgesia induced by ECS. Furthermore, it is possible that other behavioral manipulations which display only partial opiate characteristics may be mediated by H-endorphin or similar endogenous substances.
先前的研究表明，急性给予电惊厥休克（ECS）可产生强效镇痛作用，这种镇痛作用仅部分被纳洛酮逆转，但在重复给予ECS和长期给予吗啡后几乎完全耐受。为了阐明ECS镇痛的潜在机制，最近将其与一种新发现的阿片类物质——体液（H）-内啡肽的镇痛作用进行了比较。通过甩尾法测量，向大鼠脑室内（i.c.v.）注射H-内啡肽可产生剂量相关的镇痛作用。此外，连续4天每天i.c.v.注射40微克吗啡会导致对H-内啡肽的镇痛作用完全耐受。然而，纳洛酮仅能部分逆转H-内啡肽的镇痛作用。令人惊讶的是，只有较低剂量的1毫克/千克发挥了显著的拮抗作用，而较高剂量的10毫克/千克拮抗剂则没有效果。在ECS镇痛中也可以看到纳洛酮作用的类似非常规情况。在这里，用1毫克/千克纳洛酮预处理可显著减弱镇痛作用，而给予10毫克/千克拮抗剂则没有效果。相比之下，在同一动物中测量的僵住症不受1毫克/千克纳洛酮的影响，但将剂量增加到10毫克/千克会显著减弱ECS诱导的僵住症。一方面，H-内啡肽镇痛的阿片样物质性质，另一方面，H-内啡肽和ECS镇痛与纳洛酮的非常规剂量关系，表明这种阿片类物质参与了ECS诱导的镇痛作用。此外，其他仅表现出部分阿片样特征的行为操作可能是由H-内啡肽或类似的内源性物质介导的。
