Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleNEUROPHARMACOLOGY

Protein Kinase Cβ Is a Critical Regulator of Dopamine Transporter Trafficking and Regulates the Behavioral Response to Amphetamine in Mice

Rong Chen, Cheryse A. Furman, Minjia Zhang, Myung N. Kim, Robert W. Gereau IV, Michael Leitges and Margaret E. Gnegy
Journal of Pharmacology and Experimental Therapeutics March 2009, 328 (3) 912-920; DOI: https://doi.org/10.1124/jpet.108.147959
Rong Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Cheryse A. Furman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minjia Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Myung N. Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert W. Gereau IV
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Leitges
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Margaret E. Gnegy
  • 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 dopamine transporter (DAT) is a key mediator of dopaminergic neurotransmission and a major target for amphetamine. We found previously that protein kinase C (PKC) β regulates amphetamine-mediated dopamine efflux. Here, using PKCβ wild-type (WT) and knockout (KO) mice, we report a novel role for PKCβ in amphetamine-induced regulation of DAT trafficking and activity. PKCβ KO mice have less striatal surface DAT, [3H]dopamine uptake, and amphetamine-stimulated dopamine efflux, yet higher novelty-induced locomotor activity than WT mice. Although a short exposure (≤90 s) to amphetamine rapidly increases striatal surface DAT and [3H]dopamine uptake in WT mice, this treatment decreases surface DAT and [3H]dopamine uptake in KO mice. Increases in surface DAT and [3H]dopamine uptake are not evident in KO mice until a longer exposure (60 min) to amphetamine, by which time WT mice exhibit decreased surface DAT and dopamine uptake. The slowness of amphetamine-induced striatal DAT trafficking in PKCβ KO mice was mimicked by the use of a specific PKCβ inhibitor, LY379196, in WT mice. Furthermore, PKCβ KO mice exhibit reduced locomotor responsiveness to amphetamine compared with WT, which could be explained by reduced surface DAT and delayed amphetamine-induced DAT trafficking in KO mice. Our results indicate that PKCβ is crucial for proper trafficking of DAT to the surface and for functioning of DAT and amphetamine signaling, providing new insight into the role of PKCβ as an important regulator of dopaminergic homeostasis.

Footnotes

  • This study has been supported by the National Institutes of Health National Institute on Drug Abuse [Grant DA11697]; and by the National Institutes of Health National Institute of Neurological Disorders and Stroke [Grant NS48602].

  • doi:10.1124/jpet.108.147959.

  • ABBREVIATIONS: DAT, dopamine transporter; DA, dopamine; AMPH, amphetamine; PKC, protein kinase C; BIM I, bisindoylmaleimide I; KO, knockout; WT, wild type; KRB, Krebs-Ringer bicarbonate; WIN 35,428, 2β-carbomethoxy-3β-(4-fluorophenyl)tropane; Veh, vehicle; ANOVA, analysis of variance; LY, LY379196; Sal, saline; V, Veh; A, AMPH; Ro31-8220, bisindolylmaleimide IX.

    • Received October 26, 2008.
    • Accepted December 16, 2008.
  • 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.
Back to top

In this issue

Journal of Pharmacology and Experimental Therapeutics: 377 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 377, Issue 2
1 May 2021
  • Table of Contents
  • About the Cover
  • 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.
Protein Kinase Cβ Is a Critical Regulator of Dopamine Transporter Trafficking and Regulates the Behavioral Response to Amphetamine in Mice
(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

Protein Kinase Cβ Is a Critical Regulator of Dopamine Transporter Trafficking and Regulates the Behavioral Response to Amphetamine in Mice

Rong Chen, Cheryse A. Furman, Minjia Zhang, Myung N. Kim, Robert W. Gereau, Michael Leitges and Margaret E. Gnegy
Journal of Pharmacology and Experimental Therapeutics March 1, 2009, 328 (3) 912-920; DOI: https://doi.org/10.1124/jpet.108.147959

Citation Manager Formats

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

Protein Kinase Cβ Is a Critical Regulator of Dopamine Transporter Trafficking and Regulates the Behavioral Response to Amphetamine in Mice

Rong Chen, Cheryse A. Furman, Minjia Zhang, Myung N. Kim, Robert W. Gereau, Michael Leitges and Margaret E. Gnegy
Journal of Pharmacology and Experimental Therapeutics March 1, 2009, 328 (3) 912-920; DOI: https://doi.org/10.1124/jpet.108.147959
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike 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

  • CVN424, a novel GPR6 inverse agonist for Parkinson's disease
  • Methylone Brain Concentrations and Pharmacodynamic Effects
  • Oxysterols and Ethanol
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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics