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
Research ArticleNeuropharmacology

Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine

Kenichi Fukumoto, Hidetoh Toki, Michihiko Iijima, Takashi Hashihayata, Jun-ichi Yamaguchi, Kenji Hashimoto and Shigeyuki Chaki
Journal of Pharmacology and Experimental Therapeutics April 2017, 361 (1) 9-16; DOI: https://doi.org/10.1124/jpet.116.239228
Kenichi Fukumoto
Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan (K.F., H.T., M.I., T.H., J.Y., S.C.); and Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (K.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hidetoh Toki
Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan (K.F., H.T., M.I., T.H., J.Y., S.C.); and Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (K.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michihiko Iijima
Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan (K.F., H.T., M.I., T.H., J.Y., S.C.); and Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (K.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takashi Hashihayata
Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan (K.F., H.T., M.I., T.H., J.Y., S.C.); and Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (K.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jun-ichi Yamaguchi
Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan (K.F., H.T., M.I., T.H., J.Y., S.C.); and Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (K.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenji Hashimoto
Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan (K.F., H.T., M.I., T.H., J.Y., S.C.); and Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (K.H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shigeyuki Chaki
Research Headquarters, Taisho Pharmaceutical Co., Ltd., Saitama, Japan (K.F., H.T., M.I., T.H., J.Y., S.C.); and Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan (K.H.)
  • 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

This article has a correction. Please see:

  • Correction to “Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine” - July 01, 2017

Abstract

The rapid-acting and long-lasting antidepressant effects of (R,S)-ketamine have recently gained much attention. Although (S)-ketamine has been studied as an active isomer, recent evidence suggests that (R)-ketamine exhibits longer-lasting antidepressant effects than (S)-ketamine in rodents. However, the antidepressant potential of (R)-ketamine has not been fully addressed. In the present study, we compared the antidepressant effects of (R)-ketamine with those of (S)-ketamine in animal models of depression, including a model that is refractory to current medications. Both (R)-ketamine and (S)-ketamine exhibited antidepressant effects at 30 minutes as well as at 24 hours after administration in forced-swimming and tail-suspension tests in mice. At 48 hours after administration, however, (R)-ketamine still exerted a significant antidepressant effect in the tail-suspension test, whereas the effect of (S)-ketamine was no longer observed. Moreover, (R)-ketamine, but not (S)-ketamine, significantly reversed the depressive-like behavior induced by repeated treatments with corticosterone in rats at 24 hours after a single administration. This effect was attenuated by an α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor antagonist, suggesting the involvement of AMPA receptor stimulation in the effects. Both (R)-ketamine and (S)-ketamine exhibited practically the same exposure levels in plasma, brain, and cerebrospinal fluid in mice and rats, and both compounds were rapidly eliminated from plasma (<4–8 hours). The present results confirmed the previous findings that (R)-ketamine exerted longer-lasting antidepressant effects than (S)-ketamine in animal models of depression. Moreover, our study is the first to demonstrate that (R)-ketamine exerted a sustained antidepressant effect even in a model that is refractory to currently prescribed antidepressants.

Footnotes

    • Received November 24, 2016.
    • Accepted January 18, 2017.
  • K.F., H.T., M.I., T.H., J.Y., and S.C. are full-time employees of Taisho Pharmaceutical Co., Ltd.

  • dx.doi.org/10.1124/jpet.116.239228.

  • Copyright © 2017 by 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: 361 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 361, Issue 1
1 Apr 2017
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • 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 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.
Antidepressant Potential of (R)-Ketamine in Rodent Models: Comparison with (S)-Ketamine
(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 ArticleNeuropharmacology

Antidepressant Effects of (R)-Ketamine

Kenichi Fukumoto, Hidetoh Toki, Michihiko Iijima, Takashi Hashihayata, Jun-ichi Yamaguchi, Kenji Hashimoto and Shigeyuki Chaki
Journal of Pharmacology and Experimental Therapeutics April 1, 2017, 361 (1) 9-16; DOI: https://doi.org/10.1124/jpet.116.239228

Citation Manager Formats

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

Share
Research ArticleNeuropharmacology

Antidepressant Effects of (R)-Ketamine

Kenichi Fukumoto, Hidetoh Toki, Michihiko Iijima, Takashi Hashihayata, Jun-ichi Yamaguchi, Kenji Hashimoto and Shigeyuki Chaki
Journal of Pharmacology and Experimental Therapeutics April 1, 2017, 361 (1) 9-16; DOI: https://doi.org/10.1124/jpet.116.239228
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • VTA Muscarinic M5 Receptors and Effort-Choice Behavior
  • Substituted Tryptamine Activity at 5-HT Receptors and SERT
  • KRM-II-81 Analogs
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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics