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
OtherNEUROPHARMACOLOGY

Electrophysiological Characterization of the Effect of Long-Term Duloxetine Administration on the Rat Serotonergic and Noradrenergic Systems

Lynne E. Rueter, Claude De Montigny and Pierre Blier
Journal of Pharmacology and Experimental Therapeutics May 1998, 285 (2) 404-412;
Lynne E. Rueter
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Claude De Montigny
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pierre Blier
  • 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

Duloxetine is a dual serotonin (5-HT)/norepinephrine (NE) reuptake blocker with antidepressant potential. In the present in vivo electrophysiological study, the changes in the function of the rat 5-HT and NE systems after 2- and 21-day administration of duloxetine (20 mg/kg/day) were assessed in the dorsal hippocampus and the dorsal raphe nucleus (DRN). The firing rate of DRN neurons was decreased after 2 days of duloxetine, but returned to the control level after 21-day administration. This recovery of firing rate was presumably due to the desensitization of the DRN somatodendritic 5-HT1A autoreceptors found after long-term duloxetine administration. Overall serotonergic tone was assessed by examining the ability of the 5-HT1A antagonist WAY 100635 to alter hippocampal firing. WAY 100635 increased hippocampal firing rates in 21-day treated rats to a greater extent than in 2-day treated or control rats, suggesting that long-term administration induced an increase in endogenous levels of 5-HT in postsynaptic regions. This increase in 5-HT levels was accompanied by selective changes in the 5-HT and NE systems induced by long-term duloxetine administration,i.e., the desensitization of the alpha-2 adrenergic heteroreceptor on 5-HT terminals and the continued blockade of the 5-HT transporters. In contrast, the sensitivity of thealpha-2 adrenergic and terminal 5-HT1Bautoreceptors, as well as that of the postsynaptic 5-HT1Areceptor after 21-day treatment was unchanged. Therefore, this study demonstrates that duloxetine increases serotonergic tone in a limbic forebrain structure and may therefore be effective in the treatment of depression.

Footnotes

  • Send reprint requests to: Dr. Lynne Rueter, Neurobiological Psychiatry Unit, McGill University, 1033 Pine Avenue West, Montréal, Québec, Canada H3A 1A1.

  • ↵1 This work was supported in part by the Medical Research Council of Canada (Grants MT-6444 and MA-11014) and the Fonds de la Recherche en Santé du Québec. L.R. is the recipient of a Fellowship from the Royal Victoria Hospital Research Institute (Montréal, Canada). P.B. is the recipient of a Medical Research Council of Canada Scientist Award.

  • Abbreviations:
    5-HT
    5-hydroxytryptamine (serotonin)
    NE
    norepinephrine
    SSRI
    selective serotonin reuptake inhibitor
    LSD
    lysergic acid diethylamide
    DRN
    dorsal raphe nucleus
    MAOI
    monoamine oxidase inhibitor
    SIL
    silence
    ANOVA
    analysis of variance
    • Received August 6, 1997.
    • Accepted January 9, 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.
Electrophysiological Characterization of the Effect of Long-Term Duloxetine Administration on the Rat Serotonergic and Noradrenergic Systems
(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
OtherNEUROPHARMACOLOGY

Electrophysiological Characterization of the Effect of Long-Term Duloxetine Administration on the Rat Serotonergic and Noradrenergic Systems

Lynne E. Rueter, Claude De Montigny and Pierre Blier
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 404-412;

Citation Manager Formats

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

Share
OtherNEUROPHARMACOLOGY

Electrophysiological Characterization of the Effect of Long-Term Duloxetine Administration on the Rat Serotonergic and Noradrenergic Systems

Lynne E. Rueter, Claude De Montigny and Pierre Blier
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 404-412;
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 and Materials
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • D1 agonist vs. methylphenidate on PFC working memory
  • Iclepertin (BI 425809) in schizophrenia-related models
  • Obesity Thwarts Preconditioning in TBI
Show more Neuropharmacology

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