RATIONALE: 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. OBJECTIVES: 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. CONCLUSION: 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.
RATIONALE: 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. OBJECTIVES: 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. CONCLUSION: 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.
Authors: S Couillard-Despres; C Wuertinger; M Kandasamy; M Caioni; K Stadler; R Aigner; U Bogdahn; L Aigner Journal: Mol Psychiatry Date: 2009-01-13 Impact factor: 15.992
Authors: Iva Dincheva; Jianmin Yang; Anfei Li; Tina Marinic; Helena Freilingsdorf; Chienchun Huang; B J Casey; Barbara Hempstead; Charles E Glatt; Francis S Lee; Kevin G Bath; Deqiang Jing Journal: Am J Psychiatry Date: 2017-10-31 Impact factor: 18.112
Authors: Stal Saurav Shrestha; Eric E Nelson; Jeih-San Liow; Robert Gladding; Chul Hyoung Lyoo; Pam L Noble; Cheryl Morse; Ioline D Henter; Jeremy Kruger; Bo Zhang; Stephen J Suomi; Per Svenningsson; Victor W Pike; James T Winslow; Ellen Leibenluft; Daniel S Pine; Robert B Innis Journal: Am J Psychiatry Date: 2014-03 Impact factor: 18.112
Authors: Lauritz R Meyer; Benjamin Dexter; Cecilia Lo; Elizabeth Kenkel; Takahito Hirai; Robert D Roghair; Sarah E Haskell Journal: J Matern Fetal Neonatal Med Date: 2017-04-24
Authors: Yasmina Molero; Paul Lichtenstein; Johan Zetterqvist; Clara Hellner Gumpert; Seena Fazel Journal: PLoS Med Date: 2015-09-15 Impact factor: 11.069
Authors: Marco A Bottelier; Marieke L J Schouw; Anne Klomp; Hyke G H Tamminga; Anouk G M Schrantee; Cheima Bouziane; Michiel B de Ruiter; Frits Boer; Henricus G Ruhé; Damiaan Denys; Roselyne Rijsman; Ramon J L Lindauer; Hans B Reitsma; Hilde M Geurts; Liesbeth Reneman Journal: BMC Psychiatry Date: 2014-02-19 Impact factor: 3.630