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Chronic fluoxetine treatment alters behavior, but not adult hippocampal neurogenesis, in BALB/cJ mice

Molecular Psychiatry volume 13, pages 119–121 (2008)Cite this article

Chronic antidepressant treatment has been shown to increase adult hippocampal neurogenesis.1 In recent years, it has been widely suggested that the clinical effects of antidepressants may be mediated through an increase in adult hippocampal neurogenesis.2 This hypothesis is attractive because the delay between stimulating cell proliferation and the production of mature neurons might explain the delayed onset of the clinical effects of antidepressant drugs. In support of this hypothesis, it has been shown that hippocampal neurogenesis is required for the behavioral effects of chronic antidepressants in mice.2 However, a recent report has cast doubt on these findings.3 Given the potential importance of this hypothesis, it is necessary to replicate these studies. Here, we use three well-established, behavioral tests of antidepressant action (novelty-suppressed feeding (NSF), open field test and marble burying) and three markers of neurogenesis (bromodeoxyuridine (BrdU), Ki-67 and doublecortin (DCX)) to re-evaluate this hypothesis.

Previous studies have suggested that BALB/cJ mice are especially sensitive to the behavioral effects of fluoxetine treatment.4 First, we administered fluoxetine to BALB/cJ mice for 14 days (10 mg per kg per day, delivered by Alzet osmotic pump subcutaneously; n=6 per group). BrdU, a thymidine analog, was injected 150 mg per kg intraperitoneally, 24 h prior to killing. We detected no increase in hippocampal cell proliferation in the dentate gyrus by either of the two markers used (Ki-67: P=0.59, t=0.55; BrdU: P=0.25, t=1.22).

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Authors and Affiliations

  1. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK

    G-J Huang & J Flint

  2. Department of Experimental Psychology, University of Oxford, Oxford, UK

    D Bannerman

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  1. G-J Huang
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  2. D Bannerman
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  3. J Flint
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Correspondence to G-J Huang.

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Huang, GJ., Bannerman, D. & Flint, J. Chronic fluoxetine treatment alters behavior, but not adult hippocampal neurogenesis, in BALB/cJ mice. Mol Psychiatry 13, 119–121 (2008). https://doi.org/10.1038/sj.mp.4002104

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