TY - JOUR
T1 - Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment
AU - Bouet, Valentine
AU - Klomp, Anne
AU - Freret, Thomas
AU - Wylezinska-Arridge, Marzena
AU - Lopez-Tremoleda, Jordi
AU - Dauphin, François
AU - Boulouard, Michel
AU - Booij, Jan
AU - Gsell, Willy
AU - Reneman, Liesbeth
PY - 2012
Y1 - 2012
N2 - 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. 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 [I-123]beta-CIT) and a novel magnetic resonance imaging (MRI) approach. 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. 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. 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
AB - 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. 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 [I-123]beta-CIT) and a novel magnetic resonance imaging (MRI) approach. 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. 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. 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
U2 - https://doi.org/10.1007/s00213-011-2580-1
DO - https://doi.org/10.1007/s00213-011-2580-1
M3 - Article
C2 - 22205158
SN - 0033-3158
VL - 221
SP - 329
EP - 339
JO - Psychopharmacology
JF - Psychopharmacology
IS - 2
ER -