Neurochemical study far psyyootropic actions of general anesthetics

为阐明全身麻醉药致精神作用的神经化学基础，本文研究了一氧化二氮对内源性大麻素系统和中枢神经系统作用的关系。大鼠分别腹腔内、脑室内、鞘内注射大麻素1受体拮抗剂利莫那班。注射利莫那班30分钟后，给动物75%的氧化亚氮，用于：甩尾试验每隔30 min进行一次，时间从0 ~ 210 min。甩尾试验的最大可能效应的百分比（%MPE）随着一氧化二氮吸入而增加。笑气给药30 min后出现效应峰值，随后%MPE逐渐下降至基线水平：对笑气镇痛作用的急性耐受性的形成。然;腹腔注射利莫那班5 mg/kg和脑室注射利莫那班10 μg时，%MPE没有从峰值水平下降，相反，%MP ...更多信息 大鼠鞘内注射10 μ g利莫那班后，E值不随笑气吸入而增加。笑气是人类长期广泛使用的吸入麻醉药，具有镇痛、欣快和药物滥用等作用。此外，在各种动物中已知对镇痛作用的急性耐受性的发展。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赏系统。本研究结果表明，腹腔注射和脑室内注射利莫那班均不能阻断氧化亚氮的中枢神经系统作用，而鞘内注射利莫那班则能拮抗氧化亚氮的镇痛作用。内源性大麻素可能与脊髓水平的一氧化二氮相互作用，大麻素参与了对一氧化二氮镇痛作用急性耐受的形成。因此，本研究的结果提供了神经化学基础的事实，花生四烯酸和一氧化二氮之间的相互作用在大脑皮层可能不同于在脊髓。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