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鞘内微量注射阿片类药物引起的不同行为效应:吗啡、美沙酮和D-丙氨酸2-甲硫氨酸-脑啡肽酰胺所致惊厥和僵住效应的比较

Differential behavioral effects induced by intrathecal microinjection of opiates: comparison of convulsive and cataleptic effects produced by morphine, methadone, and D-Ala2-methionine-enkephalinamide.

作者信息

Frenk H, Watkins L R, Mayer D J

出版信息

Brain Res. 1984 May 7;299(1):31-42. doi: 10.1016/0006-8993(84)90785-6.

Abstract

Intrathecal (i.t.) microinjection of 400 micrograms of morphine in rats induces convulsive activity restricted to the hindlimbs. This activity is potentiated rather than antagonized by naltrexone, is potentiated in animals pretreated over 6 days with increasingly higher systemic doses of morphine, and is potentiated and prolonged by high thoracic spinalization . Similar to morphine, convulsive spinal activity could also be elicited with i.t. injection of the non-opiate convulsant penthylenetetrazol (PTZ). However, methadone, D-ala2-methionine-enkephalinamide (DALA), or naltrexone, injected i.t. at equimolar doses with morphine did not produce similar convulsive behavior. DALA and methadone rather produced pronounced spinal catalepsy. It was concluded: that the spinal convulsive action of morphine is not mediated by specific opiate receptors; and that the spinal cord may be one of the sites where high doses of systemically administered morphine may produce convulsions.

摘要

给大鼠鞘内微量注射400微克吗啡会诱发仅限于后肢的惊厥活动。这种活动被纳曲酮增强而非拮抗,在接受6天以上逐渐增加全身吗啡剂量预处理的动物中被增强,并且通过高位胸段脊髓横断而增强和延长。与吗啡相似,鞘内注射非阿片类惊厥剂戊四氮(PTZ)也可引发脊髓惊厥活动。然而,以与吗啡等摩尔剂量鞘内注射美沙酮、D-丙氨酸2-甲硫氨酸脑啡肽酰胺(DALA)或纳曲酮,并未产生类似的惊厥行为。DALA和美沙酮反而产生明显的脊髓僵住症。得出的结论是:吗啡的脊髓惊厥作用不是由特定的阿片受体介导的;并且脊髓可能是全身给予高剂量吗啡可能产生惊厥的部位之一。

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