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[Effects of 5-HT2 agonist/antagonist on sleep apnea in Sprague-Dawley rats]
Yi-jue Zhong1, Cheng Zhang, Guang-fa Wang
1Department of Pulmonary Medicine, First Hospital, Peking University, Beijing 100034, China.
Objective:
To evaluate the effects of 5-HT2 agonist/antagonist Ketanserin on sleep apnea in Sprague-Dawley (SD) rats.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Both a 5-HT2 agonist and antagonist reduced sleep apnea index in rats, indicating a complex role for the 5-HT2 receptor in sleep-related breathing regulation. Further research is needed to understand the underlying mechanisms.
Area of Science:
- Neuroscience
- Sleep Medicine
- Pharmacology
Context:
- Sleep apnea is a prevalent sleep disorder characterized by recurrent episodes of respiratory obstruction.
- The 5-HT2 receptor system plays a role in regulating various physiological processes, including respiration.
Purpose:
- To investigate the effects of a 5-HT2 receptor agonist (DOI) and antagonist (Ketanserin) on sleep apnea in a rat model.
- To assess the impact of these agents on respiratory parameters and sleep architecture.
Summary:
- Microinjection of DOI (5-HT2 agonist) and Ketanserin (5-HT2 antagonist) into the fourth ventricle of Sprague-Dawley rats significantly reduced the total apnea index.
- Both compounds decreased post-sigh apnea index and spontaneous apnea index during NREM sleep, but did not affect REM sleep SPAI.
- Neither DOI nor Ketanserin altered sleep efficiency or the ratio of NREM to REM sleep.
Impact:
- These findings suggest a complex involvement of the 5-HT2 receptor in the regulation of breathing during sleep.
- The study highlights the potential of targeting the 5-HT2 receptor for sleep apnea treatment, although mechanisms require further elucidation.
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