Effects of 5-hydroxytryptamine and 5-hydroxytryptamine 2A/2C agonist on the genioglossus activity and sleep apnea in rats.
BACKGROUND
5-Hydroxytryptamine (5-HT) is a common neurotransmitter in the brain which plays an important role in the pathogenesis of sleep apnea. Dysfunction of 5-HT and 5-HT(2) receptors may lead to the collapse of the upper airway and the instability of respiratory control, which in turn produce apnea. Genioglossus (GG) is one of the most important oropharyngeal muscles maintaining the upper airway open. The present study aimed to investigate the effects of 5-HT and 5-HT(2) receptor on GG activity and the sleep apnea in Sprague-Dawley (SD) rats.


METHODS
Microinjection probes were placed within the fourth ventricle of sixteen SD rats. After recovery for a week, the electromyogram (EMG) of GG was recorded in the anesthetized and vagotomized rats. The changes of GG activity before and after the microinjection of 5-HT or 5-HT(2A/2C) agonist -2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) were observed. Probes were also laid in another eight SD rats. Electroencephalogram (EEG), EMG of neck muscle and respiration were recorded at the same time a week later. The effects of DOI on the occurrence of sleep apnea were explored.


RESULTS
Both 5-HT and DOI significantly enhanced the activity of GG just 3 minutes after the completion of injection. The effect of 5-HT disappeared quickly and the effect of DOI lasted for more than 27 minutes. DOI also significantly decreased the post-sigh apnea index in non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep and decreased the spontaneous apnea index only in NREM sleep (P < 0.05, respectively).


CONCLUSIONS
5-HT and 5-HT(2A/2C) system correlated closely with the pathogenesis of the sleep apnea syndrome and 5-HT receptors may become the target of the drug treatment.
Zhong
Yi-jue
YJ
Department of Pulmonary Medicine, Peking University First Hospital, Beijing 100034, China.
Zhang
Cheng
C
Wang
Guang-fa
GF
D000662:Amphetamines / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004569:Electroencephalography; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D012891:Sleep Apnea Syndromes / Q000188:drug therapy*; D012895:Sleep, REM / Q000187:drug effects
D000662:Amphetamines; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine