title: Prevention of seizure-induced sudden death in a chronic SUDEP model by semichronic administration of a selective serotonin reuptake inhibitor.
abstract: DBA/1 mice are a chronically susceptible model of sudden unexpected death in epilepsy (SUDEP) that exhibit chronic audiogenic generalized convulsive seizures (GCSs), leading to death from respiratory arrest (RA) if not resuscitated. Serotonin (5-HT) normally enhances respiration in response to elevated CO(2) levels, which occur during GCSs in humans. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, increase 5-HT availability. We examined whether fluoxetine can block GCS-induced sudden death in DBA/1 mice. Fluoxetine (15-70 mg/kg ip) was administered acutely with seizure induction at 30minutes or semichronically in five daily doses (20mg/kg/day) with induction after 5 days. Acute fluoxetine (45 or 70 mg/kg) significantly reduced the incidence of RA without blocking seizure susceptibility. Semichronic fluoxetine did not block seizures, but significantly reduced seizure-induced RA, which is consistent with effects of SSRIs on respiration in patients with epilepsy [Bateman LM, Li DS,LiN TC, Seyal M. Epilepsia 2010;51:2211-4]. These findings suggest that treatment with SSRIs should be evaluated for reducing the incidence of SUDEP in patients.
authors.affiliation: Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL 62794–9629, USA. cfaingold@siumed.edu
authors.forename: Carl L
authors.initials: CL
authors.lastname: Faingold
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Tupal
authors.forename: Marcus
authors.initials: M
authors.lastname: Randall
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000818:Animals; D016009:Chi-Square Distribution; D003645:Death, Sudden / Q000209:etiology* / Q000517:prevention & control*; D016757:Death, Sudden, Cardiac; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005473:Fluoxetine / Q000008:administration & dosage*; D051379:Mice; D008811:Mice, Inbred DBA; D012133:Respiratory Paralysis / Q000150:complications / Q000209:etiology / Q000517:prevention & control; D012640:Seizures / Q000150:complications* / Q000188:drug therapy / Q000209:etiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors