| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
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
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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
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