evidence supporting a role of serotonin in modulation of sudden death induced by seizures in dba2 mice purpose sudden unexpected death in epilepsy sudep is a serious concern for epilepsy patients dba2 mice are proposed as a sudep model because these mice exhibit respiratory arrest ra after audiogenic seizures agss and ra is also implicated in human sudep respiratory mechanisms are modulated in part by serotonin therefore we evaluated the effects of serotoninergic agents on ra incidence in dba2 micemethods dba2 mice 75 exhibited ags and ra and approximately 99 of animals could be resuscitated the mice exhibiting ra were given a selective serotonin reuptake inhibitor fluoxetine 24 h after the initial ags and ra susceptibility was evaluated 30 min later ten percent of dba2 mice exhibited tonic hindlimb extension te without ra and a serotonin antagonist cyproheptadine was administered to these miceresults fluoxetine 1525 mgkg ip significantly reduced the incidence of ra in dba2 mice after agss and this effect was reversible by 72 h only the 25mgkg dose reduced ags severity in mice exhibiting te without ra the incidence of ra was significantly increased 30 min after cyproheptadine 12 mgkg ip most of these mice exhibited agss without ra again by 72 hconclusions these findings indicate that fluoxetine reduced ra in dba2 mice at doses that did not reduce seizure severity because dba2 mice are a proposed model for human sudep these data support evaluation of fluoxetine for sudep prevention in the patient population most susceptible to sudep the data raise concern about the use of serotonin antagonists in this patient population