title: Alcohol withdrawal in epileptic rats - Effects on postictal depression, respiration, and death.
abstract: Patients with epilepsy are at risk of sudden unexpected death in epilepsy (SUDEP). The most common series of events in witnessed cases of SUDEP is a generalized convulsive seizure followed by terminal apnea. Risk factors for SUDEP include prolonged postictal depression (PID), as well as alcohol abuse. The present study examined these issues in a genetic epilepsy model that exhibits generalized convulsive audiogenic seizures (AGSz) but rarely exhibits seizure-induced death, the genetically epilepsy-prone rats (GEPR-9s). We evaluated the effect of ethanol withdrawal (ETX) in GEPR-9s on respiration patterns, duration of PID, and the incidence of seizure-induced death. Audiogenic seizures were induced in GEPR-9s and in normal Sprague-Dawley rats, which were subjected to a 4-day binge ethanol protocol, 18-24h after the last ethanol dose. Following the tonic seizures, all GEPR-9s exhibited PID, characterized by loss of the righting reflex and respiratory distress (RD), which were absent during ETX seizures in the normal rats. During ETX, GEPR-9s exhibited significant increases in the duration of PID and RD, compared with vehicle-treated GEPR-9s. A significant increase in the incidence of death following seizure in GEPR-9s subjected to ETX was observed, compared with that in vehicle-treated GEPR-9s and normal rats subjected to ETX. Death in GEPR-9s was preceded by prolonged seizures because, in part, of the emergence of post-tonic generalized clonus. These results indicate that ETX induced significant increases in the duration of PID and RD, which contributed to the greater incidence of mortality in GEPR-9s compared with that in vehicle-treated GEPR-9s and normal rats. These experiments observed an elevated risk of sudden death associated with alcohol withdrawal in a genetic epilepsy model that had previously been identified as a risk factor in human SUDEP.
authors.affiliation: Departments of Pharmacology and Neurology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, United States.
authors.forename: Srinivasa P
authors.initials: SP
authors.lastname: Kommajosyula
authors.affiliation: Departments of Pharmacology and Neurology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, United States.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Randall
authors.affiliation: Departments of Pharmacology and Neurology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, United States.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Tupal
authors.affiliation: Departments of Pharmacology and Neurology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, United States. Electronic address: cfaingold@siumed.edu.
authors.forename: Carl L
authors.initials: CL
authors.lastname: Faingold
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects*; D000818:Animals; D003645:Death, Sudden / Q000209:etiology*; D020195:Epilepsy, Reflex / Q000150:complications*; D000431:Ethanol / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration; D013375:Substance Withdrawal Syndrome / Q000150:complications*
chemical_list: D000431:Ethanol
keywords: Alcohol withdrawal; Audiogenic seizures; Genetically epilepsy-prone rat (GEPR-9); Postictal depression; Respiratory depression; SUDEP