AUTHOR=Vallée Nicolas , Lambrechts Kate , De Maistre Sébastien , Royal Perrine , Mazella Jean , Borsotto Marc , Heurteaux Catherine , Abraini Jacques , Risso Jean-Jacques , Blatteau Jean-Eric 

TITLE=Fluoxetine Protection in Decompression Sickness in Mice is Enhanced by Blocking TREK-1 Potassium Channel with the “spadin” Antidepressant

JOURNAL=Frontiers in Physiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2016.00042

DOI=10.3389/fphys.2016.00042

ISSN=1664-042X

ABSTRACT=<p>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 WT<sub>cont</sub> 46 WT<sub>flux</sub> 30 HET<sub>flux</sub> and 46 KO<sub>flux</sub>) constituting the flux-pool and 113 supplementary mice (27 KO-like 24 WT<sub>flux2</sub> 24 KO-like<sub>flux</sub> 21 WT<sub>cont2</sub> 17 WT<sub>no dive</sub>) constituting the spad-pool were included in this study. Only 7% of KO-TREK-1 treated with fluoxetine (KO<sub>flux</sub>) and 4% of mice treated with both spadin and fluoxetine (KO-like<sub>flux</sub>) 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.</p>