Abstracts

Rationale: Deficits in cardiorespiratory and/or arousal function can potentially lead to seizure-induced respiratory arrest (apnea), the leading cause of sudden unexpected death in epilepsy (SUDEP). Our preceding studies demonstrated that elevated norepinephrine (NE) function by atomoxetine, an NE reuptake inhibitor, reduces seizure-induced apnea, which is mediated by α2 adrenoceptors in DBA/1 mice. However, it is unknown if other adrenoceptors contribute to suppressing seizure-induced apnea in DBA/1 mice. It was reported that β2 adrenoceptors are involved in arousal. This study aimed to investigate the effects of systemic injection of clenbuterol, a β2 adrenoceptor agonist, on seizure-induced mortality, apnea and seizure activities in DBA/1 mice.

Methods: DBA/1 mice were primed at postnatal day 26 by daily acoustic stimulation (96 dB SPL) for 3-4 days. Primed DBA/1 mice are consistently susceptible to seizure-induced apnea, which can be resuscitated for reuse in experiments using a rodent ventilator. The susceptibility of a primed DBA/1 mouse to seizure-induced apnea was confirmed 24 hr prior to the experiment. Clenbuterol, ICI-118,551 (a β2 antagonist), atomoxetine, salbutamol (a β2 agonist) or vehicle was intraperitoneally (i.p.) administered 45-150 min prior to acoustic stimulation, and the effects of each drug or drug combination (ICI-118,551 + atomoxetine) on the incidence of seizure-induced mortality, apnea and seizures were tested and digitally recorded for offline analysis. The incidence of seizure-induced events between a drug treatment and its vehicle control or between a drug and drug combination treatments was compared using the Chi-square test.

Results: Systematic administration (i.p.) of clenbuterol at 5 mg/kg (n = 8; p < 0.01) and 10 mg/kg (n = 9;