Central deficiency of norepinephrine synthesis and norepinephrinergic neurotransmission contributes to seizure-induced respiratory arrest

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of mortality patients with intractable epilepsy. However, pathogenesis SUDEP seems to be poorly understood. Our previous findings showed that incidence seizure-induced respiratory arrest (S-IRA) was markedly reduced by atomoxetine a murine model. Because central norepinephrine ?-1 receptor (NE?-1R) plays vital role regulating function, we hypothesized suppression S-IRA mediated NE/NE?-1R interactions can reversed NE?-1R antagonism. We examined whether atomoxetine-mediated evoked either acoustic stimulation or pentylenetetrazole (PTZ) DBA/1 mice intraperitoneal (IP) and intracerebroventricular (ICV) administration prazosin, selective antagonist NE?-1R. The content activity tyrosine hydroxylase (TH), rate-limiting enzyme for NE synthesis, lower brainstem measured ELISA. Electroencephalograms (EEG) were obtained from using PTZ-evoked In our models, PTZ significantly low doses IP ICV prazosin. Neither repetitive nor TH levels brainstem. increased mechanical ventilation mice, which makes dying suffering recover. EEG data although protective effect neither drug suppressed activity. These suggest deficient synthesis norepinephrinergic neurotransmission contributed potential therapeutic target prevention SUDEP.