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
OtherANALGESIA AND DRUGS OF ABUSE

Cannabinoid-Precipitated Withdrawal: A Time-Course Study of the Behavioral Aspect and Its Correlation with Cannabinoid Receptors and G Protein Expression

Tiziana Rubino, Gabriela Patrini, Paola Massi, Domenica Fuzio, Daniela Viganò, Gabriella Giagnoni and Daniela Parolaro
Journal of Pharmacology and Experimental Therapeutics May 1998, 285 (2) 813-819;
Tiziana Rubino
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gabriela Patrini
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paola Massi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Domenica Fuzio
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniela Viganò
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gabriella Giagnoni
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniela Parolaro
  • 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

To characterize the time course of the behavioral and biochemical aspects of the cannabinoid withdrawal syndrome, we injected the cannabinoid antagonist SR141716A (5 mg/kg i.p.) in rats made tolerant to CP-55,940 (0.4 mg/kg i.p., twice daily for 6.5 days), 1, 24 and 96 h after the last CP-55,940 injection. Because the CB1 receptor and G protein alpha subunit are involved in cannabinoid tolerance, we observed their changes throughout the brain during the withdrawal syndrome by use of in situ hybridization. In vehicle-pretreated rats SR141716A per se induced abnormal behavior significantly different from the vehicle group: wet dog shakes, forepaw fluttering and scratching. These signs remained significantly elevated even after the second and third antagonist doses. SR141716A significantly modified the mRNA levels of Gαs and Gαi subunits in some brain areas without affecting CB1 receptor and Gαo expression. These findings led us to conclude that SR141716A may have intrinsic activity. Concerning cannabinoid withdrawal, the first SR141716A injection in tolerant rats resulted in behavioral signs different from those observed with the antagonist alone; this moderate withdrawal syndrome was characterized by turning, chewing and digging. Additional SR141716A doses 24 and 96 h later did not induce a significant abstinence syndrome. In situ hybridization after the first SR141716A injection showed that CB1 receptor and G protein alpha subunits, whose levels were low in tolerance, recovered their basal level of expression. Thus, the general desensitization of the cannabinoid receptor and of the transduction system in tolerance are recovered in abstinent rats and might be part of the molecular mechanisms underlying cannabinoid dependence.

Footnotes

  • Send reprint requests to: Prof. Daniela Parolaro, Institute of Pharmacology, Faculty of Sciences, University of Milan, Via Vanvitelli 32/A, 20129 Milan, Italy.

  • ↵1 This work was supported by a grant from MURST 40% 1995 and MURST 60% 1994.

  • Abbreviation:
    SR141716A
    N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide·HCl
    Δ9-THC
    Δ9-tetrahydrocannabinol
    CP-55
    940, [1α,2β-(R)-5α]-(−)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-phenol
    • Received June 2, 1997.
    • Accepted January 23, 1998.
  • 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
Vol. 285, Issue 2
1 May 1998
  • Table of Contents
  • 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.
Cannabinoid-Precipitated Withdrawal: A Time-Course Study of the Behavioral Aspect and Its Correlation with Cannabinoid Receptors and G Protein Expression
(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
OtherANALGESIA AND DRUGS OF ABUSE

Cannabinoid-Precipitated Withdrawal: A Time-Course Study of the Behavioral Aspect and Its Correlation with Cannabinoid Receptors and G Protein Expression

Tiziana Rubino, Gabriela Patrini, Paola Massi, Domenica Fuzio, Daniela Viganò, Gabriella Giagnoni and Daniela Parolaro
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 813-819;

Citation Manager Formats

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

Share
OtherANALGESIA AND DRUGS OF ABUSE

Cannabinoid-Precipitated Withdrawal: A Time-Course Study of the Behavioral Aspect and Its Correlation with Cannabinoid Receptors and G Protein Expression

Tiziana Rubino, Gabriela Patrini, Paola Massi, Domenica Fuzio, Daniela Viganò, Gabriella Giagnoni and Daniela Parolaro
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 813-819;
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
    • Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Effect of COX-1 and COX-2 Inhibition on Induction and Maintenance of Carrageenan-Evoked Thermal Hyperalgesia in Rats
  • Delta Opioid Receptor Enhancement ofMu Opioid Receptor-Induced Antinociception in Spinal Cord
  • Pharmacodynamics of a Monoclonal Antiphencyclidine Fab with Broad Selectivity for Phencyclidine-Like Drugs1
Show more ANALGESIA AND DRUGS OF ABUSE

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