Carley D W, Radulovacki M
Department of Medicine, University of Illinois College of Medicine at Chicago, 60612, USA.
Chest. 1999 May;115(5):1397-401. doi: 10.1378/chest.115.5.1397.
The aim of our study was to determine the effects of serotonin (5-HT), which does not penetrate the blood-brain barrier (BBB), and GR38032F, a 5-HT3 receptor antagonist that may cross the BBB, on spontaneous apneas in adult Sprague-Dawley rats.
Rats were implanted with electrodes for EEG and electromyographic recording to monitor sleep, with a radiotelemetry transmitter for monitoring aortic BP and heart period (HP) and were placed inside a single chamber plethysmograph for monitoring respiration. Sleep, BP, HP, and respiration were monitored for 6 h following administration of drugs. Intraperitoneal injection of 5-HT (0.79 mg/kg) to rats increased spontaneous central apneas during rapid eye movement (REM) sleep by > 250% in comparison to control recording (p = 0.01). GR38032F (0.1 mg/kg), which produced no effect on apnea expression, completely blocked the 5-HT-induced increase in REM apneas. Administration of 5-HT did not affect apnea expression in non-REM sleep and had no effect on sleep or BP.
From these observations, we conclude that binding at 5-HT3 receptors in the peripheral nervous system promotes REM-related apnea genesis in rats. These findings further suggest that endogenous 5-HT, acting at least at peripheral 5-HT3 receptors, may play a baseline physiologic role in the expression of spontaneous central apneas in rats.
我们研究的目的是确定无法穿透血脑屏障（BBB）的血清素（5-羟色胺，5-HT）以及可能穿过血脑屏障的5-HT3受体拮抗剂GR38032F对成年Sprague-Dawley大鼠自发性呼吸暂停的影响。
给大鼠植入用于脑电图（EEG）和肌电图记录以监测睡眠的电极、用于监测主动脉血压（BP）和心动周期（HP）的无线电遥测发射器，并将其置于单室体积描记器内以监测呼吸。给药后6小时监测睡眠、血压、心动周期和呼吸情况。与对照记录相比，给大鼠腹腔注射5-HT（0.79毫克/千克）可使快速眼动（REM）睡眠期间的自发性中枢性呼吸暂停增加超过250%（p = 0.01）。对呼吸暂停表现无影响的GR38032F（0.1毫克/千克）完全阻断了5-HT诱导的REM期呼吸暂停增加。5-HT给药对非REM睡眠中的呼吸暂停表现无影响，对睡眠或血压也无影响。
根据这些观察结果，我们得出结论，外周神经系统中5-HT3受体的结合促进了大鼠REM相关呼吸暂停的发生。这些发现进一步表明，内源性5-HT，至少作用于外周5-HT3受体，可能在大鼠自发性中枢性呼吸暂停的表现中发挥基线生理作用。
