Effects of 5-HT2 agonist/antagonist on sleep apnea in Sprague-Dawley rats

Abstract

To evaluate the effects of 5-HT2 agonist/antagonist Ketanserin on sleep apnea in Sprague-Dawley (SD) rats. Twenty adult male SD rats were operated for implantation of EEG and EMG electrodes and a microinjection probe was placed within the fourth ventricle. After recovery for a week, rats were monitored for sleep and respiration in three continuous days. There is no intervention on the first day. Before monitoring, 40 microl ACSF were microinjected into the IV ventricle of the rats on the second day. On the third day before monitoring, 40 microl DOI were microinjected into the IV ventricle of ten rats and 40 microl Ketanserin into another ten ones. Compared with blank control and microinjection of ACSF, DOI significantly reduced the total apnea index (AI) from 18.3 (11.1, 20.3) times/h and 15.2 (11.4, 18.0) times/h to 10.8 (3.1, 14.1) times/h (P=0.005 and 0.005, respectively). Post sign apnea index (PSAI) during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep as well as spontaneous apnea index (SPAI) during NREM sleep were all significantly decreased; (P<0.05, respectively); while it had no effect on SPAI during REM sleep (P>0.05). Neither sleep efficiency (the percent of total sleep time in total monitoring time) nor the time ratio of NREM sleep and REM sleep was significantly changed. In contrast to blank control and microinjection of ACSF, Ketanserin significantly reduced the total apnea index (AI) from 19.2 (13.7, 20.9) times/h and 19.0 (12.9, 21.6) times/h to 13.1 (9.5, 14.9) times/h (P=0.005 and 0.005, respectively). PSAI during NREM and REM sleep were significantly decreased (P<0.05, respectively). SPAI during NREM and REM sleep were changed without statistically significant (P>0.05, respectively). It also had no effects on sleep efficiency and the time ratio of NREM sleep and REM sleep. Both 5-HT2 agonist and antagonist decreased the sleep apnea index and had no effects on sleep structure. It shows that the role of 5-HT2 receptor in the respiratory regulation during sleep is complex. The mechanisms involved remain to be studied in future.