Antidepressant effects of ERbeta-selective estrogen receptor modulators in the forced swim test

Pharmacology, Biochemistry, and Behavior
Alicia A WalfCheryl A Frye

Abstract

Estradiol (E2) may influence depressive symptomology of women and decrease depressive behavior among rodents. The mechanism(s) for E2's antidepressant effects are not well understood. To determine whether antidepressant effects of E2 may involve actions at intracellular estrogen receptor (ER) alpha or beta isoforms, selective ER modulators (SERMs) were administered (10 microg sc) to ovariectomized rats 48 h before testing in the forced swim test, an animal model of depression, and the horizontal crossing task. Rats received sesame oil vehicle, 17beta-E2, which has a high affinity for ERalpha and ERbeta, SERMs that vary in their activity at ERalpha and beta, or a tricyclic antidepressant (desipramine; 30 mg/kg ip), as a positive control. ERalpha-selective SERMs were propyl pyrazole triol (PPT) and 17alpha-E2. PPT has more selective effects at ERalpha than does 17alpha-E2, which also binds ERbeta. ERbeta-selective SERMs were diarylpropionitrile (DPN) and 7,12-dihydrocoumestan (coumestrol). DPN is more selective at ERbeta than coumestrol, which also binds ERalpha. 17beta-E2, ERbeta-selective SERMs (DPN, coumestrol), and desipramine administration produced antidepressive behavior (decreased immobility, increased struggling and swim...Continue Reading

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Citations

Dec 17, 2009·Breast Cancer Research and Treatment·Rocío SoldatiClaudia Lanari
Oct 16, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Patricia J AllenPerry F Renshaw
Mar 24, 2006·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Alicia A Walf, Cheryl A Frye
Apr 20, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Alicia A WalfCheryl A Frye
Aug 12, 2010·Behavioural Pharmacology·Erika Estrada-CamarenaAlonso Fernández-Guasti
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Oct 16, 2012·Progress in Neuro-psychopharmacology & Biological Psychiatry·Jamie Winderbaum FernandezLynn Wecker
Oct 16, 2007·Physiology & Behavior·Alicia A Walf, Cheryl A Frye
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Jul 15, 2004·Pharmacology, Biochemistry, and Behavior·Cheryl A Frye, Kassandra L Edinger
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