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17β-Estradiol-induced antidepressant-like effect in the Forced Swim Test is absent in estrogen receptor-β knockout (BERKO) mice

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Abstract

Rationale

The decrease in levels of estrogens (ER) that occurs in menopause has been correlated with depressive disorders, probably due to ER direct and/or indirect effects in the brain, where these hormones act through both genomic (i.e. interaction as transcription factors with nuclear receptors ER-α and ER-β) and non-genomic (i.e. binding with cell-membrane receptors) mechanisms. With respect to mood related disorders the interaction between ER-β and the serotonin (5-HT) system is highly relevant. 17β-Estradiol (E2) induces expression of the enzyme implicated in 5-HT synthesis - tryptophan hydroxylase (TPH), and this effect is mediated through ER-β located in 5-HT cell bodies of the dorsal raphe nucleus (DRN).

Objective

The present studies tested the hypothesis that E2 induces antidepressant-like effects in female ovariectomized (OVX) mice, and that expression of ER-β is mandatory for such effects.

Methods

The Forced Swim Test (FST) was used in three experiments to assess (a) dose response effect of E2 in outbred and inbred mouse strains, (b) length of treatment necessary for effect, (c) and role of ER-β receptors.

Results

E2 (100 or 200 μg/kg), as well as the antidepressant desipramine (DMI), significantly reduced total duration of immobility in the FST in mice from different strains. Four consecutive daily doses (200 μg/kg) were required for such effect, which was absent in mice lacking the gene coding for ER-β (BERKO mice).

Conclusion

These data suggest that E2-induced antidepressant-like effects in mice are mediated through activation of ER-β. They offer preliminary support to the hypothesis that specific compounds acting at ER-β may influence mood in postmenopausal women.

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Authors and Affiliations

  1. Department of Pharmacology, Merck Research Laboratories, Rahway, NJ, USA

    Beatriz A. Rocha, Rebecca Fleischer & Gerry J. Hickey

  2. Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, NJ, USA

    James M. Schaeffer & Susan P. Rohrer

  3. 126 Lincoln Ave, RY80Y-140, Rahway, NJ, 07065, USA

    Beatriz A. Rocha

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  1. Beatriz A. Rocha
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  2. Rebecca Fleischer
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Correspondence to Beatriz A. Rocha.

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Rocha, B.A., Fleischer, R., Schaeffer, J.M. et al. 17β-Estradiol-induced antidepressant-like effect in the Forced Swim Test is absent in estrogen receptor-β knockout (BERKO) mice. Psychopharmacology 179, 637–643 (2005). https://doi.org/10.1007/s00213-004-2078-1

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