Neurochemical study far psyyootropic actions of general anesthetics

为阐明全麻致精神作用的神经化学基础，研究了内源性大麻素系统与氧化亚氮中枢神经系统作用的关系。男性的纯种。大鼠分别给予大麻素1受体拮抗剂利莫那班，利莫那班注射后30分钟，给予75%氧化亚氮，持续180 min。尾弹试验每30分钟进行一次，从0到210分钟。在对照组中，甩尾试验的最大可能效果百分比（%MPE）随吸入氧化亚氮而增加。氧化亚氮给药30min后效果达到峰值，随后%MPE逐渐下降至基线水平：对氧化亚氮镇痛作用产生急性耐受。然而;腹腔注射利莫那班5 mg/kg，脑室注射利莫那班10 μg的大鼠，%MPE与峰值相比无明显下降；腹腔注射利莫那班10 μg的大鼠，%MPE与峰值相比无明显升高。一氧化二氮是长期以来广泛应用于人体的吸入性麻醉剂，具有镇痛、欣快和药物滥用的作用。此外，已知在各种动物中对镇痛作用产生急性耐受。内源性大麻素，anandamide，作为大麻素1受体的激动剂激活脑内多巴胺能奖励系统。本研究结果显示，腹膜内和脑室内利莫那班均未阻断氧化亚氮的中枢神经系统作用，但鞘内利莫那班可拮抗氧化亚氮的镇痛作用。内源性大麻素可能在脊柱水平与氧化亚氮相互作用；阿南达胺参与了对一氧化二氮镇痛作用的急性耐受的发展。因此，本研究的结果为大脑皮层中anandamide和氧化亚氮的相互作用可能不同于脊髓中的这一事实提供了神经化学基础。少

To clarify the neurochemical basis for psycotropic actions of general anesthetics, the relationship between the endocannabinoid system and central nervous system actions of nitrous oxide was studied.Male Wistar. rats were received cannabinoid 1 receptor antagonist, rimonabant, intraperitoneally, intraventricularly, intrathecally respectively Thirty minutes after rimonabant injection, 75% nitrous oxide was given to animals for: 180 min. The tail flick test was performed every 30 min, from 0 to 210 min.In control group, the percent of maximal possible effect (%MPE) of the tail flick test increased with nitrous oxide inhalation. The peak effects occurred after 30 min of nitrous oxide administration, and then %MPE gradually decreased to the baseline level: the development of acute tolerance to the analgesic action of nitrous oxide. However; in the group administered rimonabant 5 mg/kg intraperitoneally and 10 μg intraventricularly, %MPE did not decrease from the peak level In contrast, %MP … More E in the-rats injected rimonabant 10 μ g intrathecally did not increase with nitrous oxide inhalation.Nitrous oxide is widely used inhaled anesthetics in humans for a long time and induces analgesia, euphoria and drug abuse. In addition, the development acute tolerance to the analgesic effect is known in various animals. The endocannabinoid, anandamide, acts as an agonist on cannabinoid 1 receptor activates intracerebral dopaminergic reward system. In the results of this study, the central nervous system actions of nitrous oxide were not blocked by intraperitneal and intraventricular rimonabant However intrathecal rimonabant antagonized the analgesic action of nitrous oxide. The endocannabinoid might interact with nitrous oxide in spinal level; anandamide participated in the development of acute tolerance to the analgesic action of nitrous oxide. Therefore, the results of this study provide the neurochemical basis for the fact that interaction between anandamide and nitrous oxide in the cerebral cortex might differ from in the spinal cord. Less