Skip to main content

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
    • Special Collections
  • EDITORIAL BOARD
    • Editorial Board
    • ECR Advisory Board
    • Journal Staff
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
    • Accessibility
  • SUBSCRIBE

User menu

  • Log out
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Neuroscience
  • Log out
  • Log in
  • My Cart
Journal of Neuroscience

Advanced Search

Submit a Manuscript
  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
    • Special Collections
  • EDITORIAL BOARD
    • Editorial Board
    • ECR Advisory Board
    • Journal Staff
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
    • Accessibility
  • SUBSCRIBE
PreviousNext
ARTICLE, Behavioral/Systems

Hyperfunction of Dopaminergic and Serotonergic Neuronal Systems in Mice Lacking the NMDA Receptor ε1 Subunit

Yoshiaki Miyamoto, Kiyofumi Yamada, Yukihiro Noda, Hisashi Mori, Masayoshi Mishina and Toshitaka Nabeshima
Journal of Neuroscience 15 January 2001, 21 (2) 750-757; https://doi.org/10.1523/JNEUROSCI.21-02-00750.2001
Yoshiaki Miyamoto
1Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kiyofumi Yamada
1Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yukihiro Noda
1Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hisashi Mori
2Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masayoshi Mishina
2Department of Molecular Neurobiology and Pharmacology, School of Medicine, University of Tokyo, Tokyo 113-0033, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toshitaka Nabeshima
1Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan, and
  • 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

NMDA receptors, an ionotropic subtype of glutamate receptors (GluRs) forming high Ca2+-permeable cation channels, are composed by assembly of the GluRζ subunit (NR1) with any one of four GluRε subunits (GluRε1–4; NR2A-D). In the present study, we investigated neuronal functions in mice lacking the GluRε1 subunit. GluRε1 mutant mice exhibited a malfunction of NMDA receptors, as evidenced by alterations of [3H]MK-801 binding as well as 45Ca2+ uptake through the NMDA receptors. A postmortem brain analysis revealed that both dopamine and serotonin metabolism were increased in the frontal cortex and striatum of GluRε1 mutant mice. The NMDA-stimulated [3H]dopamine release from the striatum was increased, whereas [3H]GABA release was markedly diminished in GluRε1 mutant mice. When (+)bicuculline, a GABAA receptor antagonist, was added to the superfusion buffer, NMDA-stimulated [3H]dopamine release was significantly increased in wild-type, but not in the mutant mice. GluRε1 mutant mice exhibited an increased spontaneous locomotor activity in a novel environment and an impairment of latent learning in a water-finding task. Hyperlocomotion in GluRε1 mutant mice was attenuated by treatment with haloperidol and risperidone, both of which are clinically used antipsychotic drugs, at doses that had no effect in wild-type mice. These findings provide evidence that NMDA receptors are involved in the regulation of behavior through the modulation of dopaminergic and serotonergic neuronal systems. In addition, our findings suggest that GluRε1 mutant mice are useful as an animal model of psychosis that is associated with NMDA receptor malfunction and hyperfunction of dopaminergic and serotonergic neuronal systems.

  • NMDA receptor
  • GluRε1 subunit
  • dopaminergic neuronal system
  • serotonergic neuronal system
  • hyperlocomotion
  • schizophrenia
View Full Text
Back to top

In this issue

The Journal of Neuroscience: 21 (2)
Journal of Neuroscience
Vol. 21, Issue 2
15 Jan 2001
  • Table of Contents
  • Index by author
Email

Thank you for sharing this Journal of Neuroscience 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.
Hyperfunction of Dopaminergic and Serotonergic Neuronal Systems in Mice Lacking the NMDA Receptor ε1 Subunit
(Your Name) has forwarded a page to you from Journal of Neuroscience
(Your Name) thought you would be interested in this article in Journal of Neuroscience.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
Hyperfunction of Dopaminergic and Serotonergic Neuronal Systems in Mice Lacking the NMDA Receptor ε1 Subunit
Yoshiaki Miyamoto, Kiyofumi Yamada, Yukihiro Noda, Hisashi Mori, Masayoshi Mishina, Toshitaka Nabeshima
Journal of Neuroscience 15 January 2001, 21 (2) 750-757; DOI: 10.1523/JNEUROSCI.21-02-00750.2001

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Request Permissions
Share
Hyperfunction of Dopaminergic and Serotonergic Neuronal Systems in Mice Lacking the NMDA Receptor ε1 Subunit
Yoshiaki Miyamoto, Kiyofumi Yamada, Yukihiro Noda, Hisashi Mori, Masayoshi Mishina, Toshitaka Nabeshima
Journal of Neuroscience 15 January 2001, 21 (2) 750-757; DOI: 10.1523/JNEUROSCI.21-02-00750.2001
Twitter logo Facebook 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

Keywords

  • NMDA receptor
  • GluRε1 subunit
  • dopaminergic neuronal system
  • serotonergic neuronal system
  • hyperlocomotion
  • schizophrenia

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

ARTICLE

  • Functional Hemichannels in Astrocytes: A Novel Mechanism of Glutamate Release
  • Evidence for Long-Lasting Cholinergic Control of Gap Junctional Communication between Adrenal Chromaffin Cells
  • Menstrual Cycle-Dependent Neural Plasticity in the Adult Human Brain Is Hormone, Task, and Region Specific
Show more ARTICLE

Behavioral/Systems

  • The Role of Rat Medial Frontal Cortex in Effort-Based Decision Making
  • Isolation of Relevant Visual Features from Random Stimuli for Cortical Complex Cells
  • Genetic Dissociation of Opiate Tolerance and Physical Dependence in δ-Opioid Receptor-1 and Preproenkephalin Knock-Out Mice
Show more Behavioral/Systems
  • Home
  • Alerts
  • Follow SFN on BlueSky
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Issue Archive
  • Collections

Information

  • For Authors
  • For Advertisers
  • For the Media
  • For Subscribers

About

  • About the Journal
  • Editorial Board
  • Privacy Notice
  • Contact
  • Accessibility
(JNeurosci logo)
(SfN logo)

Copyright © 2025 by the Society for Neuroscience.
JNeurosci Online ISSN: 1529-2401

The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in JNeurosci.