期刊
ANESTHESIA AND ANALGESIA
卷 108, 期 2, 页码 491-495出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1213/ane.0b013e31819000c8
关键词
-
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [17390423, 17591608, 18591684]
- Grants-in-Aid for Scientific Research [18591684, 17390423, 17591608] Funding Source: KAKEN
BACKGROUND: Orexins (OXs) regulate wakefulness, and a lack of OX Type-I receptors cause narcolepsy. OX selectively increases norepinephrine (NE) release from rat cerebral cortical slices, and brain noradrenergic neurons are involved in the sleep-wakefulness cycle. Ketamine increases NE release from the rat cerebral cortex. We hypothesized that OX Would affect ketamine anesthesia's interactions with brain noradrenergic neuronal activity. METHODS: We used Sprague Dawley rats. We Studied 1) in vivo effects of orexin A (OXA) and SB-334867-A (Orexin-1 receptor antagonist) on ketamine-induced anesthesia time, 2) in vivo effects of OXA on ketamine-induced increase in NE release from the frontal cortex assessed using microdialysis, and 3) in vitro effects of ketamine on OXA-evoked NE release from rat cerebrocortical slices. RESULTS: 1) Intracerebroventricular OXA 1 nmol significantly decreased ketamine anesthesia time by 20%-30% at 50, 100, and 125 mg/kg intraperitoneal (IP) ketamine. SB-334867-A fully reversed the decrease produced by OXA. 2) OXA also decreased the release of NE induced by ketamine even though OXA increased the release of NE in rat prefrontal cortex. Maximum NE release in Group OX + K (intracerebroventricular OXA 1. nmol + IP ketamine 100 mg/kg) was 271% and was significantly smaller than that in Group K (ketamine 1.00 mg/kg IP, 390% of baseline, P = 0.029). 3) Ketamine inhibited OX-evoked NE release with clinically relevant IC50 values. CONCLUSION: Orexinergic neurons may be an important target for ketamine. OXA antagonized ketamine anesthesia via Orexin-1 receptor with noradrenergic neurons.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据