SEROTONIN 5-HT3-RECEPTOR ANTAGONIST GR 38032F SUPPRESSES SLEEP APNEASIN RATS

The effects of administration of GR38032F, a 5-HT3 receptor antagonist , on spontaneous sleep apneas were studied in adult Sprague-Dawley rat s by monitoring sleep, respiration and blood pressure for 6 hours. Int raperitoneal injection of GR38032F (1mg/kg) suppressed spontaneous cen tral apneas during non-rapid-eye-movement (NREM) and especially during rapid-eye-movement (REM) sleep. This effect was associated with incre ased 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 GR3803 2 (Yoshioka et al, JPET 1992; 260:917-924). Our data implicate 5-HT3 r eceptor systems in determining sleep-related respiratory drive and apn ea expression in rats, effects which are most probably mediated by vag al afferents.