Role of Peripheral Serotonin in the Regulation of Central Sleep Apneas in Rats

Abstract

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.