Fluoxetine prevents respiratory arrest without enhancing ventilation in DBA/1 mice

Epilepsy & Behavior : E&B
Chang ZengHua-Jun Feng

Abstract

Sudden unexpected death in epilepsy (SUDEP) is a fatal epileptic event. DBA/1 mice are a relevant animal model for the study of SUDEP, as these mice exhibit seizure-induced respiratory arrest (S-IRA) leading to death, which has been observed in patients with witnessed SUDEP. Fluoxetine, a selective serotonin (5-hydroxytryptamine or 5-HT) reuptake inhibitor (SSRI), reduces S-IRA in DBA/1 mice. Given that DBA/1 mice with S-IRA can be resuscitated using a ventilator, we hypothesized that breathing stimulants can prevent S-IRA and that fluoxetine prevents S-IRA by enhancing ventilation in these mice. Spontaneous respiratory function in anesthetized or awake DBA/1 mice was examined using noninvasive plethysmography before and after administering fluoxetine or breathing stimulants, doxapram, and 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (PK-THPP). The effects of these drugs on S-IRA in DBA/1 mice were tested. As reported previously, systemic administration of fluoxetine reduced S-IRA in awake DBA/1 mice, but fluoxetine in anesthetized and awake DBA/1 mice did not increase basal ventilation or the ventilatory response to 7% CO2. Both doxapram and PK-THPP increased ventilation in room air and in air+7% CO2 in anesthetized DBA/1 mice. H...Continue Reading

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Citations

Aug 15, 2015·Epilepsy & Behavior : E&B·Hua-Jun Feng, Carl L Faingold
Apr 1, 2016·Expert Review of Neurotherapeutics·Aline P PansaniFulvio A Scorza
Oct 28, 2016·The Journal of Physiology·Leonardo T TotolaThiago S Moreira
May 17, 2017·Epilepsy & Behavior : E&B·Norberto Garcia-CairascoJosé A Cortes de Oliveira
Jan 9, 2019·Frontiers in Neurology·Benton S PurnellGordon F Buchanan
Dec 24, 2019·Experimental Neurology·Alexandra N PetrucciGordon F Buchanan
Mar 26, 2021·Frontiers in Neuroscience·Eric R WengertManoj K Patel

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