Ketamine and MK-801 decrease acetylcholine release in the pontine reticular formation, slow breathing, and disrupt sleep.
Ketamine and MK-801 decrease acetylcholine release in the pontine reticular formation, slow breathing, and disrupt sleep.
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DOI：
10.1093/sleep/25.6.615
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发表时间：
2002-09
期刊：
影响因子：
5.6
通讯作者：
R. Lydic;H. Baghdoyan
中科院分区：
文献类型：
--
作者：
R. Lydic;H. Baghdoyan
研究目的氯胺酮通过与n -甲基- d -天冬氨酸（NMDA）受体控制的离子通道内的苯环利定结合位点结合，诱导意识解离状态。大脑区域和神经递质系统介导氯胺酮引起的觉醒改变仍然不完全清楚。本研究使用体内微透析来验证氯胺酮改变脑桥内侧网状结构（mPRF）中乙酰胆碱（ACh）释放的假设。设计：对全身氯胺酮给药后乙酰胆碱（ACh）释放、睡眠和呼吸进行量化。微透析将nmda通道阻滞剂马来酸二唑西平（MK-801）和氯胺酮的R(-)-异构体送入mPRF，同时测量ACh的释放。设置N / A。参与者N / A。干预N / A。测量和结果：系统给予氯胺酮破坏正常睡眠周期组织，减少mPRF - ACh释放，并显著减慢呼吸速率。透析输送MK-801至mPRF显著降低呼吸频率和mPRF乙酰胆碱释放。透析输送到mPRF的R(-)-氯胺酮异构体显著降低mPRF的乙酰胆碱释放。结论系统给药氯胺酮引起的mPRF乙酰胆碱释放降低与mPRF透析递送MK-801和R(-)-氯胺酮异构体相似。这些数据与系统给予氯胺酮可能通过改变mPRF中的胆碱能神经传递而部分改变觉醒和呼吸的结论一致。
STUDY OBJECTIVES Ketamine induces a dissociated state of consciousness by binding to the phencyclidine binding site within the ion channel gated by the N-methyl-D-aspartate (NMDA) receptor. The brain regions and neurotransmitter systems mediating ketamine-induced alterations in arousal remain incompletely understood. This study used in vivo microdialysis to test the hypothesis that ketamine alters acetylcholine (ACh) release in the medial pontine reticular formation (mPRF). DESIGN Acetylcholine (ACh) release, sleep, and breathing were quantified following systemic ketamine administration. Microdialysis was used to deliver the NMDA-channel blocker dizocilpine maleate (MK-801) and the R(-)-isomer of ketamine into the mPRF while measuring ACh release. SETTING N/A. PARTICIPANTS N/A. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Systemically administered ketamine disrupted normal sleep-cycle organization, reduced mPRF ACh release, and significantly slowed rate of breathing. Dialysis delivery of MK-801 to the mPRF significantly decreased respiratory rate and mPRF ACh release. Dialysis delivery to the mPRF of the R(-)-ketamine isomer significantly decreased mPRF ACh release. CONCLUSIONS Decreased mPRF ACh release caused by systemically administered ketamine was mimicked by mPRF dialysis delivery of MK-801 and the R(-)-ketamine isomer. These data are consistent with the conclusion that systemically administered ketamine may alter arousal and breathing, in part, by altering cholinergic neurotransmission in the mPRF.