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

The Cannabinoid CB1 Antagonist N-Piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl) -4-methylpyrazole-3-carboxamide (SR-141716A) Differentially Alters the Reinforcing Effects of Heroin under Continuous Reinforcement, Fixed Ratio, and Progressive Ratio Schedules of Drug Self-Administration in Rats

M. Solinas, L. V. Panlilio, K. Antoniou, L. A. Pappas and S. R. Goldberg
Journal of Pharmacology and Experimental Therapeutics July 2003, 306 (1) 93-102; DOI: https://doi.org/10.1124/jpet.102.047928
M. Solinas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. V. Panlilio
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
K. Antoniou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
L. A. Pappas
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. R. Goldberg
  • 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

Activation or blockade of cannabinoid CB1 receptors markedly alters many effects of opioids. In the present study, we investigated whether the cannabinoid antagonist (N-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR-141716A) could alter the reinforcing effects of heroin in rats. A Δ9-tetrahydrocannabinol (THC) drug-discrimination procedure was first used to determine effective CB1 antagonist doses of SR-141716A and optimal pretreatment times for self-administration studies. Subsequently, Sprague-Dawley rats learned to self-administer heroin under three different schedules of intravenous drug injection: a continuous reinforcement schedule [fixed ratio (FR)1], a five-response, fixed ratio schedule (FR5), and a progressive ratio schedule. Then, SR-141716A (1 mg/kg i.p.) was administered 60 min before the start of the session for three consecutive daily sessions. SR-141716A markedly decreased heroin self-administration under the progressive ratio schedule at heroin doses ranging from 12.5 to 100 μg/kg/injection. In contrast, SR-141716A had no effect on heroin self-administration under the FR1 schedule at heroin doses of 50 or 100 μg/kg/injection, but produced small decreases in self-administration at lower doses (25 and 12.5 μg/kg/injection). Consistent with a behavioral economics evaluation, SR-141716A produced a small but significant decrease in self-administration of the higher 50 μg/kg/injection dose of heroin when the fixed ratio requirement was raised to five (FR5). Thus, blockade of CB1 receptors differentially decreased the reinforcing efficacy of heroin depending on the number of responses required for each injection (price). These findings indicate a facilitatory modulation of opioid reward by endogenous cannabinoid activity and provide support for the use of cannabinoid CB1 antagonists as medications for heroin addiction.

Footnotes

  • DOI: 10.1124/jpet.102.047928.

  • ABBREVIATIONS: THC, Δ9-tetrahydrocannabinol; SR-141716A, (N-piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide; CB, cannabinoid; FR, fixed ratio; ANOVA, analysis of variance.

    • Received December 20, 2002.
    • Accepted March 17, 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: 306 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 306, Issue 1
1 Jul 2003
  • 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.
The Cannabinoid CB1 Antagonist N-Piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl) -4-methylpyrazole-3-carboxamide (SR-141716A) Differentially Alters the Reinforcing Effects of Heroin under Continuous Reinforcement, Fixed Ratio, and Progressive Ratio…
(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

The Cannabinoid CB1 Antagonist N-Piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl) -4-methylpyrazole-3-carboxamide (SR-141716A) Differentially Alters the Reinforcing Effects of Heroin under Continuous Reinforcement, Fixed Ratio, and Progressive Ratio Schedules of Drug Self-Administration in Rats

M. Solinas, L. V. Panlilio, K. Antoniou, L. A. Pappas and S. R. Goldberg
Journal of Pharmacology and Experimental Therapeutics July 1, 2003, 306 (1) 93-102; DOI: https://doi.org/10.1124/jpet.102.047928

Citation Manager Formats

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

The Cannabinoid CB1 Antagonist N-Piperidinyl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl) -4-methylpyrazole-3-carboxamide (SR-141716A) Differentially Alters the Reinforcing Effects of Heroin under Continuous Reinforcement, Fixed Ratio, and Progressive Ratio Schedules of Drug Self-Administration in Rats

M. Solinas, L. V. Panlilio, K. Antoniou, L. A. Pappas and S. R. Goldberg
Journal of Pharmacology and Experimental Therapeutics July 1, 2003, 306 (1) 93-102; DOI: https://doi.org/10.1124/jpet.102.047928
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
    • 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