{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T02:06:44Z","timestamp":1773022004890,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T00:00:00Z","timestamp":1549324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100001605","name":"Epilepsy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001605","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2019,3]]},"abstract":"Summary<\/jats:title>Objective<\/jats:title>Sudden unexpected death in epilepsy (SUDEP<\/jats:styled-content>) is the leading cause of death in patients with refractory epilepsy. Although the mechanisms for SUDEP<\/jats:styled-content> are incompletely understood, seizure\u2010induced respiratory arrest (S\u2010IRA<\/jats:styled-content>) has been strongly and consistently implicated. A body of evidence indicates that serotonin (5\u2010HT<\/jats:styled-content>), a modulator of breathing, plays a critical role in SUDEP<\/jats:styled-content>. Because the 5\u2010HT<\/jats:styled-content> and norepinephrine (NE<\/jats:styled-content>) systems interact in many biologic processes and NE<\/jats:styled-content> is known to modulate breathing and seizures, we hypothesized that NE<\/jats:styled-content> may play a role in S\u2010IRA<\/jats:styled-content> and SUDEP<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>We examined the effects of pharmacologic manipulation of 5\u2010HT<\/jats:styled-content> and NE<\/jats:styled-content> on S\u2010IRA<\/jats:styled-content> and death following maximal electroshock (MES<\/jats:styled-content>)\u2013induced seizures in adult wild\u2010type (WT<\/jats:styled-content>) mice, genetically 5\u2010HT<\/jats:styled-content> neuron\u2013deficient (Lmx1b<\/jats:italic>f\/f\/p<\/jats:italic><\/jats:sup>) mice, and chemically NE<\/jats:styled-content> neuron\u2013deficient mice. Mice were treated with pharmacologic agents targeting the serotonergic and noradrenergic systems and subjected to seizure induction via MES<\/jats:styled-content> while breathing was measured via whole\u2010body plethysmography.<\/jats:p><\/jats:sec>Results<\/jats:title>S\u2010IRA<\/jats:styled-content> and death was reduced in WT<\/jats:styled-content> mice with NE<\/jats:styled-content> reuptake inhibitors (NRI<\/jats:styled-content>s), reboxetine and atomoxetine, selective serotonin reuptake inhibitors (SSRI<\/jats:styled-content>s), fluoxetine and citalopram, and the dual 5\u2010HT<\/jats:styled-content>\/NE<\/jats:styled-content> reuptake inhibitor (SNRI<\/jats:styled-content>), duloxetine. S\u2010IRA<\/jats:styled-content> and death was also reduced in Lmx1b<\/jats:italic>f\/f\/p<\/jats:italic><\/jats:sup> mice with reboxetine and fluoxetine. The protective effects of the reuptake inhibitors were prevented by the \u03b11<\/jats:sub> antagonist, prazosin. Citalopram did not reduce S\u2010IRA<\/jats:styled-content> and death in NE<\/jats:styled-content> neuron\u2013deficient mice.<\/jats:p><\/jats:sec>Significance<\/jats:title>These data suggest that 5\u2010HT<\/jats:styled-content> and NE<\/jats:styled-content> critically interact in the modulation of breathing following a seizure and potentially inform preventive strategies for SUDEP<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.14652","type":"journal-article","created":{"date-parts":[[2019,2,6]],"date-time":"2019-02-06T03:43:33Z","timestamp":1549424613000},"page":"495-507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Effect of monoamine reuptake inhibition and \u03b11<\/sub> blockade on respiratory arrest and death following electroshock\u2010induced seizures in mice"],"prefix":"10.1111","volume":"60","author":[{"given":"Stephen 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