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Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment

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Abstract

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 [123I]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.

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Acknowledgements

This work is funded by the Netherlands organization for health research and development (Veni nr. 916. 86.125), awarded to L. Reneman. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Groupe Mémoire et Plasticité comportementale (GMPc), Université de Caen Basse-Normandie, EA 4259, Caen, 14032, France

    Valentine Bouet, Thomas Freret, François Dauphin & Michel Boulouard

  2. Radiology Department, Academic Medical Center, Brain Imaging Center, Amsterdam, The Netherlands

    Anne Klomp & Liesbeth Reneman

  3. Faculty of Medicine, Biological Imaging Center, MRC Clinical Sciences Centre, Imperial College of London, 3rd floor Cyclotron Building, Hammersmith Hospital Campus, Du Cane Road, W12 0NN, London, UK

    Marzena Wylezinska-Arridge, Jordi Lopez-Tremoleda & Willy Gsell

  4. Nuclear Medicine Department, Academic Medical Center, Brain Imaging Center, Amsterdam, The Netherlands

    Jan Booij

  5. Department of Radiology, G1-241, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

    Liesbeth Reneman

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  1. Valentine Bouet
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  2. Anne Klomp
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  10. Liesbeth Reneman
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Correspondence to Liesbeth Reneman.

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Bouet, V., Klomp, A., Freret, T. et al. Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment. Psychopharmacology 221, 329–339 (2012). https://doi.org/10.1007/s00213-011-2580-1

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  • DOI: https://doi.org/10.1007/s00213-011-2580-1

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