Sood Sandeep, Raddatz Eric, Liu Xia, Liu Hattie, Horner Richard L
Department of Medicine, Rm. 6368, Medical Sciences Bldg., 1 Kings College Circle, University of Toronto, ON, Canada M5S 1A8.
J Appl Physiol (1985). 2006 Jun;100(6):1807-21. doi: 10.1152/japplphysiol.01508.2005. Epub 2006 Feb 16.
Although exogenous serotonin at the hypoglossal motor nucleus (HMN) activates the genioglossus muscle, endogenous serotonin plays a minimal role in modulating genioglossus activity in awake and sleeping rats (Sood S, Morrison JL, Liu H, and Horner RL. Am J Respir Crit Care Med 172: 1338-1347, 2005). This result therefore implies that medullary raphe neurons also play a minimal role in the normal physiological control of the HMN, but this has not yet been established because raphe neurons release other excitatory neurotransmitters onto respiratory motoneurons in addition to serotonin. This study tests the hypothesis that inhibition of medullary raphe serotonergic neurons with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) suppresses genioglossus and diaphragm activities in awake and sleeping rats. Ten rats were implanted with electrodes to record sleep-wake states and genioglossus and diaphragm activities. Microdialysis probes were also implanted into the nucleus raphe obscurus (NRO). Experiments in 10 anesthetized and vagotomized rats were also performed using the same methodology. In anesthetized rats, microdialysis perfusion of 0.1 mM 8-OH-DPAT into the NRO decreased genioglossus activity by 60.7+/-9.0% and diaphragm activity by 13.3+/-3.4%. Diaphragm responses to 7.5% CO2 were also significantly reduced by 8-OH-DPAT. However, despite the robust effects observed in anesthetized and vagotomized rats, there was no effect of 0.1 mM 8-OH-DPAT on genioglossus or diaphragm activities in conscious rats awake or asleep. The results support the concept that endogenously active serotonergic medullary raphe neurons play a minimal role in modulating respiratory motor activity across natural sleep-wake states in freely behaving rodents. This result has implications for pharmacological strategies aiming to manipulate raphe neurons and endogenous serotonin in obstructive sleep apnea.
尽管舌下运动核（HMN）处的外源性5-羟色胺可激活颏舌肌，但内源性5-羟色胺在调节清醒和睡眠大鼠的颏舌肌活动中作用极小（Sood S、Morrison JL、Liu H和Horner RL。《美国呼吸与危重症医学杂志》172: 1338 - 1347，2005年）。因此，这一结果意味着延髓中缝核神经元在HMN的正常生理控制中也起极小作用，但这一点尚未得到证实，因为中缝核神经元除了释放5-羟色胺外，还向呼吸运动神经元释放其他兴奋性神经递质。本研究检验了以下假设：用8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）抑制延髓中缝5-羟色胺能神经元可抑制清醒和睡眠大鼠的颏舌肌和膈肌活动。对10只大鼠植入电极以记录睡眠-觉醒状态以及颏舌肌和膈肌活动。还将微透析探针植入中缝隐核（NRO）。使用相同方法对10只麻醉和迷走神经切断的大鼠进行了实验。在麻醉大鼠中，向NRO微透析灌注0.1 mM 8-OH-DPAT可使颏舌肌活动降低60.7±9.0%，膈肌活动降低13.3±3.4%。8-OH-DPAT也显著降低了膈肌对7.5%二氧化碳的反应。然而，尽管在麻醉和迷走神经切断的大鼠中观察到了明显效果，但0.1 mM 8-OH-DPAT对清醒或睡眠的清醒大鼠的颏舌肌或膈肌活动没有影响。这些结果支持了这样一种观点，即内源性活跃的延髓中缝5-羟色胺能神经元在自由活动的啮齿动物的自然睡眠-觉醒状态下调节呼吸运动活动中作用极小。这一结果对旨在操纵中缝核神经元和内源性5-羟色胺治疗阻塞性睡眠呼吸暂停的药理学策略具有启示意义。
