Orexin A Decreases Ketamine-Induced Anesthesia Time in the Rat: The Relevance to Brain Noradrenergic Neuronal Activity
Orexin A Decreases Ketamine-Induced Anesthesia Time in the Rat: The Relevance to Brain Noradrenergic Neuronal Activity
复制标题
DOI：
10.1213/ane.0b013e31819000c8
复制
发表时间：
2009-02-01
影响因子：
5.7
通讯作者：
Hirota, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Tose, Ryuji;Kushikata, Tetsuya;Hirota, Kazuyoshi
背景：食欲素（OXs）调节清醒，缺乏OX - 1型受体导致嗜睡症。OX选择性地增加了大鼠大脑皮质片的去甲肾上腺素（NE）释放，脑去甲肾上腺素能神经元参与了睡眠-觉醒周期。氯胺酮增加大鼠大脑皮层释放NE。我们假设OX会影响氯胺酮麻醉与脑去甲肾上腺素能神经元活动的相互作用。方法：采用大鼠。我们研究了1)体内食欲素A （OXA）和SB-334867-A （orexin -1受体拮抗剂）对氯胺酮诱导的麻醉时间的影响，2)体内OXA对氯胺酮诱导的额叶皮层NE释放增加的影响，以及3)体外氯胺酮对OXA诱导的大鼠脑皮质片NE释放的影响。结果：1)50mg /kg、100mg /kg、125mg /kg腹腔注射氯胺酮时，脑室注射oxa1nmol可显著减少氯胺酮麻醉时间20% ~ 30%。SB-334867-A完全逆转了OXA产生的下降。2)尽管OXA增加了大鼠前额皮质NE的释放，但OXA也降低了氯胺酮诱导的NE的释放。OX + K组最大NE释放量（脑室内OXA）nmol + IP氯胺酮100 mg/kg)为271%，显著低于K组（氯胺酮1.00 mg/kg IP，为基线的390%，P = 0.029）。3)氯胺酮抑制ox诱发的NE释放，IC50值具有临床相关性。结论：食欲能神经元可能是氯胺酮的重要作用靶点。OXA通过Orexin-1受体与去甲肾上腺素能神经元拮抗氯胺酮麻醉。
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.