Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are increasingly used for the treatment of depression in children. Limited data are, however, available on their effects on brain development and their efficacy remains debated. Moreover, previous experimental studies are seriously hampered in their clinical relevance.


OBJECTIVE
The aim of the present study was to investigate putative age-related effects of a chronic treatment with fluoxetine (5 mg/kg, either orally or i.p. for 3 weeks, 1 week washout) using conventional methods (behavioral testing and binding assay using [(123)I]β-CIT) and a novel magnetic resonance imaging (MRI) approach.


METHODS
Behavior was assessed, as well as serotonin transporter (SERT) availability and function through ex vivo binding assays and in vivo pharmacological MRI (phMRI) with an acute fluoxetine challenge (10 mg/kg oral or 5 mg/kg i.v.) in adolescent and adult rats.


RESULTS
Fluoxetine caused an increase in anxiety-like behavior in treated adult, but not adolescent, rats. On the binding assays, we observed increased SERT densities in most cortical brain regions and hypothalamus in adolescent, but not adult, treated rats. Finally, reductions in brain activation were observed with phMRI following treatment, in both adult and adolescent treated animals.


CONCLUSIONS
Collectively, our data indicate that the short-term effects of fluoxetine on the 5-HT system may be age-dependent. These findings could reflect structural and functional rearrangements in the developing brain that do not occur in the matured rat brain. phMRI possibly will be well suited to study this important issue in the pediatric population.
Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Basse-Normandie, Caen, France. valentine.bouet@unicaen.fr
Valentine
V
Bouet
Anne
A
Klomp
Thomas
T
Freret
Marzena
M
Wylezinska-Arridge
Jordi
J
Lopez-Tremoleda
François
F
Dauphin
Michel
M
Boulouard
Jan
J
Booij
Willy
W
Gsell
Liesbeth
L
Reneman
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D005473:Fluoxetine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors