Serotonin 5-HT3-receptor Antagonist GR 38032F Suppresses Sleep Apneas in Rats

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Abstract
The effects of administration of GR38032F, a 5-HT3 receptor antagonist, on spontaneous sleep apneas were studied in adult Sprague-Dawley rats by monitoring sleep, respiration and blood pressure for 6 hours. Intraperitoneal injection of GR38032F (1mg/kg) suppressed spontaneous central apneas during non-rapid-eye-movement (NREM) and especially during rapid-eye-movement (REM) sleep. This effect was associated with increased respiratory drive but did not cause cardiovascular changes at the dose tested. The suppressive action of GR38032F on spontaneous sleep apneas is analogous to findings in anesthetized rats in which 5-HT and 2-methyl-5-HT provoked central apneas that were antagonized by GR38032 (Yoshioka et al, JPET1992; 260:917–924). Our data implicate 5-HT3 receptor systems in determining sleep-related respiratory drive and apnea expression in rats, effects which are most probably mediated by vagal afferents.

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