title: Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the "spadin" Antidepressant.
abstract: In mice, disseminated coagulation, inflammation, and ischemia induce neurological damage that can lead to death. These symptoms result from circulating bubbles generated by a pathogenic decompression. Acute fluoxetine treatment or the presence of the TREK-1 potassium channel increases the survival rate when mice are subjected to an experimental dive/decompression protocol. This is a paradox because fluoxetine is a blocker of TREK-1 channels. First, we studied the effects of an acute dose of fluoxetine (50 mg/kg) in wild-type (WT) and TREK-1 deficient mice (knockout homozygous KO and heterozygous HET). Then, we combined the same fluoxetine treatment with a 5-day treatment protocol with spadin, in order to specifically block TREK-1 activity (KO-like mice). KO and KO-like mice were regarded as antidepressed models. In total, 167 mice (45 WTcont 46 WTflux 30 HETflux and 46 KOflux) constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WTflux2 24 KO-likeflux 21 WTcont2 17 WTno dive) constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KOflux) and 4% of mice treated with both spadin and fluoxetine (KO-likeflux) died from decompression sickness (DCS) symptoms. These values are much lower than those of WT control (62%) or KO-like mice (41%). After the decompression protocol, mice showed significant consumption of their circulating platelets and leukocytes. Spadin antidepressed mice were more likely to exhibit DCS. Nevertheless, mice which had both blocked TREK-1 channels and fluoxetine treatment were better protected against DCS. We conclude that the protective effect of such an acute dose of fluoxetine is enhanced when TREK-1 is inhibited. We confirmed that antidepressed models may have worse DCS outcomes, but concomitant fluoxetine treatment not only decreased DCS severity but increased the survival rate.
authors.affiliation: Institut de Recherche Biomédicale des Armées, Equipe Résidante de Recherche Subaquatique Opérationnelle Toulon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vallée
authors.affiliation: Institut de Recherche Biomédicale des Armées, Equipe Résidante de Recherche Subaquatique OpérationnelleToulon, France; UFR STAPS, Laboratoire Motricité Humaine Education Sport Santé, Université du Sud Toulon VarLa Garde, France.
authors.forename: Kate
authors.initials: K
authors.lastname: Lambrechts
authors.affiliation: Hôpital d'Instruction des Armées, Service de Médecine Hyperbare et Expertise Plongée Toulon, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: De Maistre
authors.affiliation: Institut de Recherche Biomédicale des Armées, Equipe Résidante de Recherche Subaquatique Opérationnelle Toulon, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Royal
authors.affiliation: Centre National de la Recherche Scientifique and Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 Valbonne, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Mazella
authors.affiliation: Centre National de la Recherche Scientifique and Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 Valbonne, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Borsotto
authors.affiliation: Centre National de la Recherche Scientifique and Université de Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275 Valbonne, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Heurteaux
authors.affiliation: Institut de Recherche Biomédicale des Armées, Equipe Résidante de Recherche Subaquatique OpérationnelleToulon, France; Département d'Anesthésiologie, Université LavalQuébec, QC, Canada; Faculté de Médecine, Université de Caen NormandieCaen, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Abraini
authors.affiliation: Institut de Recherche Biomédicale des Armées, Equipe Résidante de Recherche Subaquatique Opérationnelle Toulon, France.
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Risso
authors.affiliation: Institut de Recherche Biomédicale des Armées, Equipe Résidante de Recherche Subaquatique Opérationnelle Toulon, France.
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Blatteau
keywords: TREK-1; bubble; capillary leak; decompression sickness; depression; diapedesis; diving; kcnk2