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British Journal of Medicine and Medical Research, ISSN: 2231-0614,Vol.: 2, Issue.: 3 (July-September)

Original Research Article

Chronic Fluoxetine Administration during Different Postnatal Development Stages Leads to Stage Dependent Changes of Glial Fibrillary Acidic Protein Expression in Rat Brain


Nathalie Bock1*, Hannah Alter1, Emre Koc1, Veit Roessner2, Aribert Rothenberger1 and Till Manzke3,4

1Department of Child and Adolescent Psychiatry, Georg-August-University of Göttingen, von Siebold-Strasse 5, 37075 Göttingen, Germany.
2Department of Child and Adolescent Psychiatry, Technische Universität Dresden, Dresden, Germany.
3Department of Neuro- and Sensory Physiology, Georg-August-University of Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
4DFG Research Center Molecular Physiology of the Brain, Göttingen, Germany.


Aims: Depressive symptoms in children and adolescents are commonly treated with serotonin re-uptake inhibitors like fluoxetine. Astrocytes expressing different serotonin receptors (5-HTRs) and the serotonin transporter (5-HTT) are affected by fluoxetine administration. The study was conducted to revise whether fluoxetine treatment during postnatal brain development results in long-term changes of astroglia.
Methodology: Thus, immunohistochemistry and real-time PCR analyses were performed at different postnatal periods in rats to investigate short- and long-term changes following by a 14-day administration with fluoxetine (5 mg/kg/BW s.c. once daily).
Results: Fluoxetine-treatments from postnatal day (pd) 1-15, measured at pd 16, led to a significant reduction of GFAP gene (Gfap) in hippocampus and GFAP protein expression in the dentate gyrus and CA1 without changes at pd 90 compared to controls. Treatments from pd 21-35 resulted in a significant decrease of Gfap and protein (measured 24 hours after last injection) in striatum (putamen), frontal cortex and hippocampus. Contrary, if measured at day 90, the same treatment led to a significant increase in those regions. Later treatments from pd 50-64 did not result in significant changes in mRNA or in protein expression.
Conclusion: This study revealed a fluoxetine-sensitive period of brain astrocyte development (i.e. periadolescence) that led to structural effects, which can even be detected in adulthood. These results might be relevant for psychopharmacological treatment in children and require continuative clinical studies.

Keywords :

Astroglia; fluoxetine; brain development; GFAP/Gfap.

Full Article - PDF    Page 292-312

DOI : 10.9734/BJMMR/2012/1099

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