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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Effects of Corticotropin-Releasing Factor Receptor-1 Antagonists on the Brain Stress System Responses to Morphine Withdrawal

Javier Navarro-Zaragoza, Cristina Núñez, M. Luisa Laorden and M. Victoria Milanés
Molecular Pharmacology May 2010, 77 (5) 864-873; DOI: https://doi.org/10.1124/mol.109.062463
Javier Navarro-Zaragoza
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cristina Núñez
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Luisa Laorden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Victoria Milanés
  • 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 role of stress in drug addiction is well established. The negative affective states of withdrawal most probably involve recruitment of brain stress neurocircuitry [e.g., induction of hypothalamo-pituitary-adrenocortical (HPA) axis, noradrenergic activity, and corticotropin-releasing factor (CRF) activity]. The present study investigated t$he role of CRF receptor-1 subtype (CRF1R) on the response of brain stress system to morphine withdrawal. The effects of naloxone-precipitated morphine withdrawal on noradrenaline (NA) turnover in the paraventricular nucleus (PVN), HPA axis activity, signs of withdrawal, and c-Fos expression were measured in rats pretreated with vehicle, CP-154526 [N-butyl-N-ethyl-2,5-dimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[3,2-e]pyrimidin-4-amine], or antalarmin (selective CRF1R antagonists). Tyrosine hydroxylase-positive neurons expressing CRF1R were seen at the level of the nucleus tractus solitarius-A2 cell group in both control and morphine-withdrawn rats. CP-154526 and antalarmin attenuated the increases in body weight loss and irritability that were seen during naloxone-induced morphine withdrawal. Pretreatment with CRF1R antagonists resulted in no significant modification of the increased NA turnover at PVN, plasma corticosterone levels, or c-Fos expression that was seen during naloxone-induced morphine withdrawal. However, blockade of CRF1R significantly reduced morphine withdrawal-induced increases in plasma adrenocorticotropin levels. These results suggest that the CRF1R subtype may be involved in the behavioral and somatic signs and in adrenocorticotropin release (partially) during morphine withdrawal. However, CRF1R activation may not contribute to the functional interaction between NA and CRF systems in mediating morphine withdrawal-activation of brain stress neurocircuitry.

Footnotes

  • This work was supported by the Ministerio de Ciencia e Innovación of Spain [Grants SAF/FEDER 2006-00331, 2007-62758, 2009-07178] and Red de Trastornos Adictivos [Grant RD06/0001/1006]. J.N.-Z. was supported by a fellowship from the Ministerio de Ciencia e Innovación.

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

    doi:10.1124/mol.109.062463.

  • ABBREVIATIONS:

    CRF
    corticotropin-releasing factor
    CRFR
    CRF receptor
    CRF1R
    CRF receptor-1 subtype
    HPA
    hypothalamus-pituitary-adrenocortical
    NA
    noradrenaline
    PVN
    paraventricular nucleus
    TH
    tyrosine hydroxylase
    NTS
    nucleus tractus solitarius
    CeA
    central amygdala
    AP
    area postrema
    DAB
    diaminobenzidine
    MHPG
    3-methoxy-4-hydroxyphenylethylen glycol
    HPLC
    high-performance liquid chromatography
    ANOVA
    analysis of variance
    CP-154526
    N-butyl-N-ethyl-2,5-dimethyl-7-(2,4,6-trimethylphenyl)pyrrolo[3,2-e]pyrimidin-4-amine
    AVP
    arginine-vasopressin
    CRA1000
    [2-[N-(2-methylthio-4-isopropylphenyl)-N-ethylamino]-4-[4-(3-fluorophenyl)-1,2,3,6-tetrahydropyridin-1-yl]-6-methylpyrimidine)]
    R121919
    3-[6-(dimethylamino)-4-methyl-pyrid-3-yl]-2,5-dimethyl-N,N-dipropyl-pyrazolo[2,3-a]pyrimidin-7-amine.

    • Received November 16, 2009.
    • Accepted February 16, 2010.
  • Copyright © 2010 The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm 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

Molecular Pharmacology: 77 (5)
Molecular Pharmacology
Vol. 77, Issue 5
1 May 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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 Molecular Pharmacology 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.
Effects of Corticotropin-Releasing Factor Receptor-1 Antagonists on the Brain Stress System Responses to Morphine Withdrawal
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Effects of Corticotropin-Releasing Factor Receptor-1 Antagonists on the Brain Stress System Responses to Morphine Withdrawal

Javier Navarro-Zaragoza, Cristina Núñez, M. Luisa Laorden and M. Victoria Milanés
Molecular Pharmacology May 1, 2010, 77 (5) 864-873; DOI: https://doi.org/10.1124/mol.109.062463

Citation Manager Formats

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

Share
Research ArticleArticle

Effects of Corticotropin-Releasing Factor Receptor-1 Antagonists on the Brain Stress System Responses to Morphine Withdrawal

Javier Navarro-Zaragoza, Cristina Núñez, M. Luisa Laorden and M. Victoria Milanés
Molecular Pharmacology May 1, 2010, 77 (5) 864-873; DOI: https://doi.org/10.1124/mol.109.062463
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
  • Benzbromarone relaxes airway smooth muscle via BK activation
Show more Articles

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 Molecular Pharmacology
  • 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
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics