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
OtherBEHAVIORAL PHARMACOLOGY

Phencyclidine-Induced Deficits in Prepulse Inhibition of Startle are Blocked by Prazosin, an Alpha-1 Noradrenergic Antagonist

Vaishali P. Bakshi and Mark A. Geyer
Journal of Pharmacology and Experimental Therapeutics November 1997, 283 (2) 666-674;
Vaishali P. Bakshi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mark A. Geyer
  • 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

Prepulse inhibition (PPI) is a form of plasticity of the startle response in which presentation of a weak stimulus immediately before an intense startling stimulus reduces the resultant startle response. Deficits in PPI, an operational measure of sensorimotor gating, are observed in schizophrenia patients and can be modeled in rats by the psychotogen phencyclidine (PCP). PCP-induced deficits in PPI in rats are resistant to dopamine and serotonin antagonists but can be antagonized by antipsychotics such as clozapine, olanzapine and Seroquel. These latter antipsychotics have antagonistic actions at several receptors, including alpha-1 and alpha-2 adrenergic, M1 muscarinic and γ-aminobutyric acid (GABA)-A receptors. Although the direct actions of PCP are thought to be mediated by noncompetitive antagonism of N-methyl-D-aspartate sites, PCP thereby indirectly activates multiple neurotransmitter systems, including those affected by the aforementioned antipsychotics. The present studies examined the possibility that an antagonist action at a particular receptor subtype might be responsible for the interaction between PCP and the clozapine-like antipsychotics by testing whether a selective antagonist at alpha-1, alpha-2, M1 or GABA-A receptors would prevent the PCP-induced deficit in PPI in rats. Animals were pretreated with either the alpha-1 antagonist prazosin (0, 0.5, 1.0 or 2.5 mg/kg), the alpha-2 antagonist RX821002 (0, 0.2 or 0.4 mg/kg), the M1 muscarinic antagonist pirenzepine (0, 10 or 30 mg/kg) or the GABA-A antagonist pitrazepin (0, 1.0 or 3.0 mg/kg) and then treated with either saline or PCP (1.5 mg/kg). Because prazosin was effective in blocking the effects of PCP, an additional experiment tested the possibility that prazosin (0, 1.0 or 2.5 mg/kg) would block the PPI deficits produced by the dopamine agonist apomorphine (0 or 0.5 mg/kg). After drug administration, animals were tested in startle chambers. PCP was found repeatedly to decrease PPI. Prazosin (1.0 and 2.5 mg/kg) blocked this deficit in two separate experiments but did not increase base-line PPI levels. The effects on PPI were dissociable from changes in startle reactivity. Furthermore, prazosin did not antagonize apomorphine-induced disruptions of PPI, which suggests that the antagonism of the PCP effect was not simply due to a generalized improvement of deficient PPI. The antagonists foralpha-2, for M1 and for GABA-A receptors had no effect on base-line PPI or on PCP-induced disruptions in PPI. These findings indicate that the PPI-disruptive effect of PCP may be mediated in part by alpha-1 adrenergic receptors and that antagonism ofalpha-1 receptors may play a major role in mediating the blockade of PCP-induced deficits in PPI by certain antipsychotics.

Footnotes

  • Send reprint requests to: Mark A. Geyer, Department of Psychiatry, 0804, University of California at San Diego, La Jolla, CA 92093-0804.

  • ↵1 This work was supported in part by Grant MH42228 from the National Institute of Mental Health and Grant DA02925 from the National Institute on Drug Abuse.

  • ↵2 Supported by Grant F31-MH11636 from the National Institute of Mental Health.

  • ↵3 Supported by a Research Scientist Award (K05-MH01223) from the National Institute of Mental Health.

  • Abbreviations:
    PCP
    phencyclidine
    PPI
    prepulse inhibition
    NMDA
    N-methyl-D-aspartate
    DA
    dopamine
    NE
    norepinephrine
    5-HT
    serotonin
    GABA
    γ-aminobutyric acid
    M1
    muscarinic 1
    AAALAC
    Association for the Assessment and Accreditation of Laboratory Animal Care
    • Received March 6, 1997.
    • Accepted July 25, 1997.
  • 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. 283, Issue 2
1 Nov 1997
  • 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.
Phencyclidine-Induced Deficits in Prepulse Inhibition of Startle are Blocked by Prazosin, an Alpha-1 Noradrenergic Antagonist
(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
OtherBEHAVIORAL PHARMACOLOGY

Phencyclidine-Induced Deficits in Prepulse Inhibition of Startle are Blocked by Prazosin, an Alpha-1 Noradrenergic Antagonist

Vaishali P. Bakshi and Mark A. Geyer
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 666-674;

Citation Manager Formats

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

Share
OtherBEHAVIORAL PHARMACOLOGY

Phencyclidine-Induced Deficits in Prepulse Inhibition of Startle are Blocked by Prazosin, an Alpha-1 Noradrenergic Antagonist

Vaishali P. Bakshi and Mark A. Geyer
Journal of Pharmacology and Experimental Therapeutics November 1, 1997, 283 (2) 666-674;
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

  • Role of residues S426 and S430 in cannabinoid tolerance
  • DAT ligands on Cocaine-Food Choice in Monkeys
  • MDPV high-responders to evaluate candidate medications
Show more Behavioral Pharmacology

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