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
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
    • 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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleBEHAVIORAL PHARMACOLOGY

Nicotinic Receptor-Mediated Reduction in l-DOPA-Induced Dyskinesias May Occur via Desensitization

Tanuja Bordia, Carla Campos, J. Michael McIntosh and Maryka Quik
Journal of Pharmacology and Experimental Therapeutics June 2010, 333 (3) 929-938; DOI: https://doi.org/10.1124/jpet.109.162396
Tanuja Bordia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carla Campos
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
J. Michael McIntosh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maryka Quik
  • 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

l-DOPA-induced dyskinesias in Parkinson's disease are a significant clinical problem for which few therapies are available. We recently showed that nicotine reduces l-DOPA-induced abnormal involuntary movements (AIMs) in parkinsonian animals, suggesting it may be useful for the treatment of l-DOPA-induced dyskinesias. The present experiments were performed to understand the mechanisms whereby nicotine reduces l-DOPA-induced AIMs. We used a well established model of dyskinesias, l-DOPA-treated unilateral 6-hydroxydopamine-lesioned rats. Dose-ranging studies showed that injection of 0.1 mg/kg nicotine once or twice daily for 4 or 10 days most effectively reduced AIMs, with no worsening of parkinsonism. Importantly, a single nicotine injection did not reduce AIMs, indicating that nicotine's effect is caused by long-term rather than short-term molecular changes. Administration of the metabolite cotinine did not reduce AIMs, suggesting a direct effect of nicotine. Experiments with the nicotinic receptor (nAChR) antagonist mecamylamine were done to determine whether nicotine acted via a receptor-mediated mechanism. Unexpectedly, several days of mecamylamine injection (1.0 mg/kg) alone significantly ameliorated dyskinesias to a comparable extent as nicotine. The decline in AIMs with combined nicotine and mecamylamine treatment was not additive, suggesting that nicotine exerts its effects via a nAChR interaction. This latter finding, combined with data showing that mecamylamine reduced AIMs to a similar extent as nicotine, and that nicotine or mecamylamine treatment both decreased α6β2* and increased α4β2* nAChR expression, suggests that the nicotine-mediated improvement in l-DOPA-induced AIMs may involve a desensitization block. These data have important implications for the treatment of l-DOPA-induced dyskinesias in Parkinson's disease.

Footnotes

  • This work was supported by the National Institutes of Health [Grants NS42091, NS47162, MH53631, DA12242].

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

    doi:10.1124/jpet.109.162396.

  • ABBREVIATIONS:

    AIM
    abnormal involuntary movement
    ANOVA
    analysis of variance
    α-CtxMII
    α-conotoxinMII
    6-OHDA
    6-hydroxydopamine
    CNS
    central nervous system
    nAChR
    nicotinic receptor
    BSA
    bovine serum albumin
    [125I]RTI-121
    [125I]2β-carboxylic acid isopropyl ester-3 β-(4-iodophenyl)tropane.

  • Received October 5, 2009.
  • Accepted March 2, 2010.
  • Copyright © 2010 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.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 382 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 382, Issue 2
1 Aug 2022
  • 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.
Nicotinic Receptor-Mediated Reduction in l-DOPA-Induced Dyskinesias May Occur via Desensitization
(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

Nicotinic Receptor-Mediated Reduction in l-DOPA-Induced Dyskinesias May Occur via Desensitization

Tanuja Bordia, Carla Campos, J. Michael McIntosh and Maryka Quik
Journal of Pharmacology and Experimental Therapeutics June 1, 2010, 333 (3) 929-938; DOI: https://doi.org/10.1124/jpet.109.162396

Citation Manager Formats

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

Share
Research ArticleBEHAVIORAL PHARMACOLOGY

Nicotinic Receptor-Mediated Reduction in l-DOPA-Induced Dyskinesias May Occur via Desensitization

Tanuja Bordia, Carla Campos, J. Michael McIntosh and Maryka Quik
Journal of Pharmacology and Experimental Therapeutics June 1, 2010, 333 (3) 929-938; DOI: https://doi.org/10.1124/jpet.109.162396
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Daily Methocinnamox and Fentanyl Self-Administration
  • Abuse Potential of Botanical Cannabidiol
  • Efficacy as a Determinant of Hyperlocomotion by MOR Ligands
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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics