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Updated: Aug 21, 2026

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear
11:17

Extinction Training During the Reconsolidation Window Prevents Recovery of Fear

Published on: August 24, 2012

Extinction memory improvement by the metabolic enhancer methylene blue

F Gonzalez-Lima1, Aleksandra K Bruchey

  • 1Institute for Neuroscience and Department of Psychology, University of Texas at Austin, Austin, Texas 78712, USA. gonzalez-lima@psy.utexas.edu

Learning & Memory (Cold Spring Harbor, N.Y.)
|October 7, 2004
PubMed

Insights

Methylene blue (MB) administration after extinction training improved memory retention in rats by boosting brain energy production. This suggests MB enhances extinction memory through increased cytochrome oxidase activity.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Extinction learning is crucial for modifying fear memories.
  • Methylene blue (MB) is a redox compound known to enhance mitochondrial function and energy production in the brain.
  • Understanding how to enhance the retention of extinction memory is important for treating fear-related disorders.

Purpose of the Study:

  • To investigate the effect of postextinction administration of methylene blue (MB) on the retention of an extinguished conditioned response.
  • To explore the underlying mechanisms, specifically the role of cytochrome oxidase activity and brain metabolic activity.

Main Methods:

  • Rats underwent tone-footshock conditioning followed by extinction training.
  • Methylene blue (MB) or saline was administered intraperitoneally for 5 days post-extinction.
  • Behavioral measures included freezing behavior (tone-evoked and pre-tone).
  • Brain metabolic activity, particularly cytochrome oxidase activity in specific prefrontal cortical regions, was assessed.

Main Results:

  • Rats treated with MB showed significantly lower postextinction freezing compared to saline controls, indicating enhanced retention of extinction memory.
  • MB treatment did not affect pre-tone freezing, motor activity, or general fearfulness, suggesting specificity of the effect.
  • MB-treated rats exhibited increased overall brain metabolic activity.
  • Higher retention of extinction in MB-treated rats correlated with increased cytochrome oxidase activity in prefrontal cortical regions (infralimbic, medial frontal, lateral orbital cortices).

Conclusions:

  • Postextinction administration of methylene blue (MB) enhances the retention of extinction memory.
  • This enhancement is associated with increased brain cytochrome oxidase activity and metabolic activity, particularly in prefrontal cortical regions.
  • MB represents a potential therapeutic agent for improving extinction memory retention.

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