Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Altered Brain Serotonin Homeostasis and Locomotor Insensitivity to 3,4-Methylenedioxymethamphetamine (“Ecstasy”) in Serotonin Transporter-Deficient Mice

Dietmar Bengel, Dennis L. Murphy, Anne M. Andrews, Christine H. Wichems, Douglas Feltner, Armin Heils, Rainald Mössner, Heiner Westphal and Klaus-Peter Lesch
Molecular Pharmacology April 1998, 53 (4) 649-655; DOI: https://doi.org/10.1124/mol.53.4.649
Dietmar Bengel
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dennis L. Murphy
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anne M. Andrews
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christine H. Wichems
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas Feltner
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Armin Heils
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rainald Mössner
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heiner Westphal
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Klaus-Peter Lesch
1 2 3
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The sodium-dependent, high affinity serotonin [5-hydroxytryptamine (5-HT)] transporter (5-HTT) provides the primary mechanism for inactivation of 5-HT after its release into the synaptic cleft. To further evaluate the function of the 5-HTT, the murine gene was disrupted by homologous recombination. Despite evidence that excess extracellular 5-HT during embryonic development, including that produced by drugs that inhibit the 5-HTT, may lead to severe craniofacial and cardiac malformations, no obvious developmental phenotype was observed in the 5-HTT−/− mice. High affinity [3H]5-HT uptake was completely absent in 5-HTT−/− mice, confirming a physiologically effective knockout of the 5-HTT gene. 5-HTT binding sites labeled with [125I]3β-(4′-iodophenyl)tropan-2β-carboxylic acid methyl ester were reduced in a gene dose-dependent manner, with no demonstrable binding in 5-HTT−/− mutants. In adult 5-HTT−/− mice, marked reductions (60–80%) in 5-HT concentrations were measured in several brain regions. While (+)-amphetamine-induced hyperactivity did not differ across genotypes, the locomotor enhancing effects of (+)-3,4-methylenedioxymethamphetamine, a substituted amphetamine that releases 5-HT via a transporter-dependent mechanism, was completely absent in 5-HTT−/− mutants. Together, these data suggest that the presence of a functional 5-HTT is essential for brain 5-HT homeostasis and for 3,4-methylenedioxymethamphetamine-induced hyperactivity.

Footnotes

    • Received August 1, 1997.
    • Accepted December 8, 1997.
  • Send reprint requests to: Klaus-Peter Lesch, M.D., Department of Psychiatry, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany. E-mail:kplesch{at}mail.uni-wuerzburg.de

  • This work was supported by the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung, the European Commission, and the Intramural Research Program of the National Institute of Mental Health. Additional assistance came from a Howard Hughes Medical Institute Fellowship for physicians (D.F.) and from support by the Hermann and Lilly Schilling Foundation (K.-P.L.).

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 53 (4)
Molecular Pharmacology
Vol. 53, Issue 4
1 Apr 1998
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Altered Brain Serotonin Homeostasis and Locomotor Insensitivity to 3,4-Methylenedioxymethamphetamine (“Ecstasy”) in Serotonin Transporter-Deficient Mice
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Altered Brain Serotonin Homeostasis and Locomotor Insensitivity to 3,4-Methylenedioxymethamphetamine (“Ecstasy”) in Serotonin Transporter-Deficient Mice

Dietmar Bengel, Dennis L. Murphy, Anne M. Andrews, Christine H. Wichems, Douglas Feltner, Armin Heils, Rainald Mössner, Heiner Westphal and Klaus-Peter Lesch
Molecular Pharmacology April 1, 1998, 53 (4) 649-655; DOI: https://doi.org/10.1124/mol.53.4.649

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Altered Brain Serotonin Homeostasis and Locomotor Insensitivity to 3,4-Methylenedioxymethamphetamine (“Ecstasy”) in Serotonin Transporter-Deficient Mice

Dietmar Bengel, Dennis L. Murphy, Anne M. Andrews, Christine H. Wichems, Douglas Feltner, Armin Heils, Rainald Mössner, Heiner Westphal and Klaus-Peter Lesch
Molecular Pharmacology April 1, 1998, 53 (4) 649-655; DOI: https://doi.org/10.1124/mol.53.4.649
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Antimicrobial and Antileukemic Transportan 10 Conjugates
  • Pharmacological characterization of zebrafish H1 receptor
  • Bhave and Forman
Show more Article

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics