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

Interaction of the Nicotinic Cholinergic System with Ethanol Withdrawal

Christopher M. Butt, Nathan M. King, Jerry A. Stitzel and Allan C. Collins
Journal of Pharmacology and Experimental Therapeutics February 2004, 308 (2) 591-599; DOI: https://doi.org/10.1124/jpet.103.059758
Christopher M. Butt
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathan M. King
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jerry A. Stitzel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allan C. Collins
  • 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 observation that alcohol and nicotine are commonly abused together suggests that the two drugs have common sites of action. In vitro studies indicate that nicotinic acetylcholine receptor (nAChR) function is enhanced by ethanol. Furthermore, some ethanol-related behaviors are associated with a region of mouse chromosome 2 that contains the gene encoding the α4 subunit of the nAChR (Chrna4). We have identified a polymorphism in Chrna4 that results in an alanine (A) or threonine (T) residue at position 529 in the second intracellular loop of the protein. Nicotinic receptors expressing the A variant have greater responses to nicotine and ethanol than receptors with the T variant when measured in vitro, but the possible effects of the polymorphism on the severity of ethanol withdrawal have not been assessed. The handling-induced convulsion (HIC) assay is an established method for studying drug withdrawal in vivo. We monitored the HIC responses of mice for 8 h after an injection of ethanol (4 g/kg). A survey of 16 mouse strains, as well as previously published data, indicated an association of the A/T polymorphism with ethanol withdrawal. This association was also found in wild-type animals from an F2 intercross of the A/J (A529-genotype) strain with C57BL/6J (T529-genotype) mice that also lack expression of the β2 nAChR subunit. β2 –/– animals, which do not express α4β2 nAChRs in the brain, exhibited significantly lower HIC responses and no effect of the polymorphism. These results suggest that the nicotinic cholinergic system and the A/T polymorphism modulate ethanol withdrawal.

Footnotes

  • This work was supported by National Institute on Alcohol Abuse and Alcoholism Grants AA11156 (to A.C.C.), AA13465 (to C.M.B.), a National Institute on Drub Abuse Research Scientist Award (DA00197; to A.C.C.), DA14369 (to J.A.S.), and a grant from the Alcoholic Beverage Medical Research Foundation (to J.A.S.). Production of the β2 null mutants was supported by DA015663.

  • DOI: 10.1124/jpet.103.059758.

  • ABBREVIATIONS: nAChR, nicotinic acetylcholine receptor; Chrna4, gene encoding the α4 nAChR subunit; Chrnb2, gene encoding the β2 nAChR subunit; HIC, handling-induced convulsion; QTL, quantitative trait loci.

    • Received September 10, 2003.
    • Accepted November 5, 2003.
  • 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: 308 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 308, Issue 2
1 Feb 2004
  • 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 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.
Interaction of the Nicotinic Cholinergic System with Ethanol Withdrawal
(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

Interaction of the Nicotinic Cholinergic System with Ethanol Withdrawal

Christopher M. Butt, Nathan M. King, Jerry A. Stitzel and Allan C. Collins
Journal of Pharmacology and Experimental Therapeutics February 1, 2004, 308 (2) 591-599; DOI: https://doi.org/10.1124/jpet.103.059758

Citation Manager Formats

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

Interaction of the Nicotinic Cholinergic System with Ethanol Withdrawal

Christopher M. Butt, Nathan M. King, Jerry A. Stitzel and Allan C. Collins
Journal of Pharmacology and Experimental Therapeutics February 1, 2004, 308 (2) 591-599; DOI: https://doi.org/10.1124/jpet.103.059758
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
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Varenicline and epibatidine as opioid adjuvants
  • MCAM reverses and prevents fentanyl ventilatory depression
  • Kv7 opener SCR2682 alleviates pain
Show more Behavioral Pharmacology

Similar Articles

  • 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