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Updated: May 30, 2026

Elevated Plus Maze for Mice
09:09

Elevated Plus Maze for Mice

Published on: December 22, 2008

A novel elevated plus-maze procedure to avoid the one-trial tolerance problem.

Peggy Schneider1, Ying-Jui Ho, Rainer Spanagel

  • 1Institute of Psychopharmacology, Central Institute of Mental Health Mannheim, Germany.

Frontiers in Behavioral Neuroscience
|August 17, 2011
PubMed
Summary
This summary is machine-generated.

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Re-testing rodents in the elevated plus-maze (EPM) is challenging due to one-trial tolerance. A 28-day interval and room change reinstated anxiolytic effects of midazolam in the EPM test.

Area of Science:

  • Neuroscience
  • Behavioral Pharmacology
  • Animal Models

Background:

  • The elevated plus-maze (EPM) is a common test for rodent anxiety.
  • One-trial tolerance (OTT) hinders re-testing by reducing open arm exploration after initial exposure, even with anxiolytics.
  • A reliable EPM re-test paradigm is needed to enhance its utility.

Purpose of the Study:

  • To investigate if extending the inter-trial interval (ITI) to 28 days and changing the testing room can overcome one-trial tolerance in the EPM.
  • To determine if these modifications restore the anxiolytic-like effects of benzodiazepines upon re-exposure.

Main Methods:

  • Wistar rats underwent two EPM trials separated by 28 days.
  • Animals received vehicle or midazolam (0.25 mg/kg) before the second trial.
Keywords:
memorymidazolammotivationone-trial tolerancere-test EPM

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Last Updated: May 30, 2026

Elevated Plus Maze for Mice
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Published on: December 22, 2008

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  • The second trial was conducted in either the same or a different testing room.

    • Main Results:

    • Open arm time in vehicle-treated rats was similar across trials and rooms.
    • Midazolam's anxiolytic-like effect (increased open arm time) was observed in the second trial only when the testing room was changed.
    • Changing the testing room and extending the ITI to 28 days prevented one-trial tolerance.

    Conclusions:

    • An inter-trial interval of 28 days combined with a change of testing room is effective in preventing one-trial tolerance in the EPM.
    • This modified re-test paradigm successfully reinstates the anxiolytic-like actions of benzodiazepines, improving the EPM's reliability.