Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleBehavioral Pharmacology

Chronic Methadone Treatment Shows a Better Cost/Benefit Ratio than Chronic Morphine in Mice

Johan Enquist, Madeline Ferwerda, Laura Milan-Lobo and Jennifer L. Whistler
Journal of Pharmacology and Experimental Therapeutics February 2012, 340 (2) 386-392; DOI: https://doi.org/10.1124/jpet.111.187583
Johan Enquist
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Madeline Ferwerda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura Milan-Lobo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer L. Whistler
  • 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

Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

Footnotes

  • This study was supported in part by a long-term fellowship from Svenska Stiftelsen för Medicinsk Forskning (to J.E.); a Shrödinger fellowship from the Austrian Science Fund [J2967-B09] (to L.M.L.); the National Institutes of Health National Institute on Drug Abuse [Grant DA019958] (to J.L.W.); and funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (to J.L.W.).

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    http://dx.doi.org/10.1124/jpet.111.187583.

  • ABBREVIATIONS:

    MOR
    μ-opiate receptor
    DMOR
    degrading MOR
    DOR
    δ-opiate receptor
    WT
    wild type
    ANOVA
    analysis of variance
    NMDA
    N-methyl-d-aspartate
    WDS
    wet dog shakes
    PT
    paw tremor
    ED50
    effective dose at 50%.

  • Received September 1, 2011.
  • Accepted November 4, 2011.
  • Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 340 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 340, Issue 2
1 Feb 2012
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics 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.
Chronic Methadone Treatment Shows a Better Cost/Benefit Ratio than Chronic Morphine in Mice
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleBehavioral Pharmacology

Methadone Causes Fewer Side Effects than Morphine

Johan Enquist, Madeline Ferwerda, Laura Milan-Lobo and Jennifer L. Whistler
Journal of Pharmacology and Experimental Therapeutics February 1, 2012, 340 (2) 386-392; DOI: https://doi.org/10.1124/jpet.111.187583

Citation Manager Formats

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

Methadone Causes Fewer Side Effects than Morphine

Johan Enquist, Madeline Ferwerda, Laura Milan-Lobo and Jennifer L. Whistler
Journal of Pharmacology and Experimental Therapeutics February 1, 2012, 340 (2) 386-392; DOI: https://doi.org/10.1124/jpet.111.187583
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Behavioral Battery for Testing Candidate Analgesics in Mice I
  • Behavioral Battery for Testing Candidate Analgesics II
  • Concentration-Response Analysis Human Taste Discrimination
Show more Behavioral Pharmacology

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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics