Journal article
Effect of monoamine reuptake inhibition and α 1 blockade on respiratory arrest and death following electroshock-induced seizures in mice
Epilepsia (Copenhagen), Vol.60(3), pp.495-507
03/2019
DOI: 10.1111/epi.14652
PMCID: PMC6467066
PMID: 30723893
Abstract
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Although the mechanisms for SUDEP are incompletely understood, seizure-induced respiratory arrest (S-IRA) has been strongly and consistently implicated. A body of evidence indicates that serotonin (5-HT), a modulator of breathing, plays a critical role in SUDEP. Because the 5-HT and norepinephrine (NE) systems interact in many biologic processes and NE is known to modulate breathing and seizures, we hypothesized that NE may play a role in S-IRA and SUDEP.
We examined the effects of pharmacologic manipulation of 5-HT and NE on S-IRA and death following maximal electroshock (MES)-induced seizures in adult wild-type (WT) mice, genetically 5-HT neuron-deficient (Lmx1b
) mice, and chemically NE neuron-deficient mice. Mice were treated with pharmacologic agents targeting the serotonergic and noradrenergic systems and subjected to seizure induction via MES while breathing was measured via whole-body plethysmography.
S-IRA and death was reduced in WT mice with NE reuptake inhibitors (NRIs), reboxetine and atomoxetine, selective serotonin reuptake inhibitors (SSRIs), fluoxetine and citalopram, and the dual 5-HT/NE reuptake inhibitor (SNRI), duloxetine. S-IRA and death was also reduced in Lmx1b
mice with reboxetine and fluoxetine. The protective effects of the reuptake inhibitors were prevented by the α
antagonist, prazosin. Citalopram did not reduce S-IRA and death in NE neuron-deficient mice.
These data suggest that 5-HT and NE critically interact in the modulation of breathing following a seizure and potentially inform preventive strategies for SUDEP.
Details
- Title: Subtitle
- Effect of monoamine reuptake inhibition and α 1 blockade on respiratory arrest and death following electroshock-induced seizures in mice
- Creators
- Stephen W Kruse - The Iowa Neuroscience Institute, University of Iowa, Iowa City, IowaKyle G Dayton - The Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IowaBenton S Purnell - The Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IowaJared I Rosner - The Secondary Student Training Program, University of Iowa, Iowa City, IowaGordon F Buchanan - The Carver College of Medicine, University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- Epilepsia (Copenhagen), Vol.60(3), pp.495-507
- DOI
- 10.1111/epi.14652
- PMID
- 30723893
- PMCID
- PMC6467066
- NLM abbreviation
- Epilepsia
- ISSN
- 0013-9580
- eISSN
- 1528-1167
- Publisher
- United States
- Grant note
- K08 NS069667 / NINDS NIH HHS University of Iowa Graduate College Epilepsy Foundation R01 NS095842 / NINDS NIH HHS F31 NS106819 / NINDS NIH HHS Iowa Neuroscience Institute Summer Scholars Beth Levitt Tross Professorship in Epilepsy Research Iowa Center for Research by Undergraduates
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Neurology; Iowa Neuroscience Institute
- Record Identifier
- 9984070337802771
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