Fluoxetine treatment abolishes the in vitro respiratory response to acidosis in neonatal mice.
BACKGROUND
To secure pH homeostasis, the central respiratory network must permanently adapt its rhythmic motor drive to environment and behaviour. In neonates, it is commonly admitted that the retrotrapezoid/parafacial respiratory group of neurons of the ventral medulla plays the primary role in the respiratory response to acidosis, although the serotonergic system may also contribute to this response.


RESULTS
Using en bloc medullary preparations from neonatal mice, we have shown for the first time that the respiratory response to acidosis is abolished after pre-treatment with the serotonin-transporter blocker fluoxetine (25-50 µM, 20 min), a commonly used antidepressant. Using mRNA in situ hybridization and immunohistology, we have also shown the expression of the serotonin transporter mRNA and serotonin-containing neurons in the vicinity of the RTN/pFRG of neonatal mice.


CONCLUSIONS
These results reveal that the serotonergic system plays a pivotal role in pH homeostasis. Although obtained in vitro in neonatal mice, they suggest that drugs targeting the serotonergic system should be used with caution in infants, pregnant women and breastfeeding mothers.
Maturation, Plasticité, Physiologie et Pathologie de la Respiration, Unité Mixte de Recherche 6231, Centre National de la Recherche Scientifique - Université de la Méditerranée - Université Paul Cézanne, Marseille, France.
Nicolas
N
Voituron
Yuri
Y
Shvarev
Clément
C
Menuet
Michelle
M
Bevengut
Caroline
C
Fasano
Erika
E
Vigneault
Salah
S
El Mestikawy
Gérard
G
Hilaire
D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers; D005473:Fluoxetine / Q000494:pharmacology*; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics; D012119:Respiration / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D017931:DNA Primers; D005473:Fluoxetine; D012333:RNA, Messenger; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors