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Short-term treatment with the antidepressant fluoxetine triggers pyramidal dendritic spine synapse formation in rat hippocampus

Authors

  • Tibor Hajszan,

    1. Department of Obstetrics, Gynaecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, CT 06520–8063, USA
    2. Laboratory of Molecular Neurobiology, Biological Research Centre, Hungarian Academy of Sciences, Szeged, Hungary
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  • Neil J. MacLusky,

    1. Centre for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, West Haverstraw, New York, USA
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  • Csaba Leranth

    1. Department of Obstetrics, Gynaecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, CT 06520–8063, USA
    2. Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, FMB 312, New Haven, CT 06520–8063, USA
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Dr Csaba Leranth, 1Department of Obstetrics, as above.
E-mail: csaba.leranth@yale.edu

Abstract

The pathomechanism of major depressive disorder and the neurobiological basis of antidepressant therapy are still largely unknown. It has been proposed that disturbed hippocampal activity could underlie some of the cognitive and vegetative symptoms of depression, at least in part because of loss of pyramidal cell synaptic contacts, a process that is likely to be reversed by antidepressant treatment. Here we provide evidence that daily administration of the antidepressant fluoxetine to ovariectomized female rats for 5 days induces a robust increase in pyramidal cell dendritic spine synapse density in the hippocampal CA1 field, with similar changes appearing in CA3 after 2 weeks of treatment. This rapid synaptic remodelling might represent an early step in the fluoxetine-induced cascade of responses that spread across the entire hippocampal circuitry, leading to the restoration of normal function in the hippocampus. Hippocampal synaptic remodelling might provide a potential mechanism to explain certain aspects of antidepressant therapy and mood disorders, especially those associated with changes in reproductive state in women, that cannot be reconciled adequately with current theories for depression.

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