Effects of different doses of 5-HT receptor ligands on genioglossus discharge in chronic intermittent hypoxia rats

Abstract

To explore the effects of different doses of 5-HT2A/2CR agonist or 5-HT2AR antagonist on genioglossus discharge in chronic intermittent hypoxia rats. Thirty adult male Sprague-Dawley rats, each 180-200 g, were randomly divided into the normoxia group (group A, n=5) and the chronic intermittent hypoxia group (CIH group, n=25) by the random number table. The rats in the CIH group were fed in the intermittent hypoxia animal chambers, while the normoxia control group was placed in the normoxia animal chambers for 8 h per day for 4 consecutive weeks. After 28 days, 5 min×3 times of stimulation with acute intermittent hypoxia (AIH) were given and the genioglossus muscle activity were then recorded and compared before and after intravenous injection of saline (group B, n=5), the 5-HT2A/2CR agonist 30 µg/3 µl (group C, n=5) or 50 µg/5 µl group (group D, n=5), 5-HT2AR antagonist 10 µg/1 µl (group E, n=5) or 70 µg/7 µl (group F, n=5). The average peak amplitude in 60 min of genioglossus muscle activity in the CIH saline control group (group B) was significantly higher than that in the normoxia group (group A), while the genioglossus discharge in the 2 groups were (42.29 ± 1.78) µV, (25.38 ± 0.89) µV respectively (P<0.01). The 5-HT2A/2CR agonist (30 µg/3 µl or 50 µg/5 µl) caused the amplitude of genioglossus muscle activity firstly to increase and then to decrease, with the peak changes showing statistical difference (P<0.05). 10 µg/1 µl 5-HT2AR antagonist did not influence genioglossus muscle activity (P>0.05), however, after intravenous injection of 70 µg/7 µl 5-HT2AR antagonist, the amplitude of genioglossus discharge firstly decreased and then gradually returned to baseline level, the difference being statistically significant, P<0.01. Our results indicate that CIH strengthens the genioglossus discharge in CIH rats. The 5-HT2A/2CR agonist can strengthen the genioglossus discharge but the 5-HT2AR antagonists can weaken the effect, both of which have dose-related effects.