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Vol. 82, No. 2, 2005
Issue release date: February 2006
Section title: Original Paper
Neuroendocrinology 2005;82:111–120
(DOI:10.1159/000091206)

Differential Protective Properties of Estradiol and Tamoxifen against Methamphetamine-Induced Nigrostriatal Dopaminergic Toxicity in Mice

D’Astous M. · Mickley K.R. · Dluzen D.E. · Di Paolo T.
aMolecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL, and Faculty of Pharmacy, Laval University, Quebec City, Canada, and bDepartment of Anatomy, Northeastern Ohio Universities College of Medicine (NEOUCOM), Rootstown, Ohio, USA

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 7/7/2005
Accepted: 11/24/2005
Published online: 2/22/2006

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN

Abstract

Mechanisms implicated in protective potential of estrogens are poorly understood. Tamoxifen, a selective estrogen receptor modulator (SERM), presents a neuroprotective effect against methamphetamine (MA)- and methoxy-phenyltetrahydropyridine (MPTP)-induced toxicity when used alone but abolishes estrogen’s positive effects when combined with this hormone. In order to understand tamoxifen’s protective properties, the present study compared it to estradiol on several markers of dopaminergic neurons to achieve a relatively comprehensive comparison between these two agents. Estradiol benzoate (E) or tamoxifen were used at different concentrations (E: 1, 10 or 40 µg; tamoxifen: 12.5, 125 or 500 µg) 24 h prior to a MA injection in ovariectomized CD-1 mice. The effects of the lesion and treatments were studied on striatal dopamine (DA) concentrations, dopamine and monoamine vesicular transporters (DAT and VMAT2), and preproenkephalin (PPE) mRNA levels. Both treatments, at all concentrations, prevented the MA-induced decrease of striatal DA concentrations and VMAT2 binding. Only E was able to prevent loss of DAT binding in the lateral striatum and to attenuate the MA-induced increase in striatal PPE mRNA levels (at 1 or 40 µg). Therefore, in this paradigm, E and tamoxifen differentially modulated MA-induced neuronal damages. While both treatments prevented the DA decrease, E protected more efficiently other dopaminergic parameters suggesting that overall E is more effective than tamoxifen as a neuroprotectant of the nigrostriatal dopaminergic system.


  

Author Contacts

Thérèse Di Paolo
Molecular Endocrinology and Oncology Research Center
Laval University Medical Center, CHUL
2705 Laurier Blvd, Quebec G1V 4G2 (Canada)
Tel. +1 418 654 2296, Fax +1 418 654 2761, E-Mail therese.dipaolo@crchul.ulaval.ca

  

Article Information

Received: July 7, 2005
Accepted after revision: November 24, 2005
Published online: January 27, 2006
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 0, Number of References : 52

  

Publication Details

Neuroendocrinology (International Journal for Basic and Clinical Studies on Neuroendocrine Relationships)

Vol. 82, No. 2, Year 2005 (Cover Date: February 2006)

Journal Editor: Kordon, C. (Paris)
ISSN: 0028–3835 (print), 1423–0194 (Online)

For additional information: http://www.karger.com/NEN


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 7/7/2005
Accepted: 11/24/2005
Published online: 2/22/2006

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 0

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: http://www.karger.com/NEN


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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