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Extinction Memory Improvement by the Metabolic Enhancer Methylene Blue

Overview
Journal Learn Mem
Specialty Neurology
Date 2004 Oct 7
PMID 15466319
Citations 45
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Abstract

We investigated whether postextinction administration of methylene blue (MB) could enhance retention of an extinguished conditioned response. MB is a redox compound that at low doses elevates cytochrome oxidase activity, thereby improving brain energy production. Saline or MB (4 mg/kg intraperitoneally) were administered to rats for 5 d following extinction training of tone-footshock conditioning. Postextinction freezing was lower in rats receiving MB compared with saline, suggesting that MB improved retention of the extinction memory. The MB effect was specific to tone-evoked freezing because there were no differences in pretone freezing. Control subjects similarly injected with MB showed no evidence of nonspecific effects on measures of motor activity and fearfulness. MB-treated rats exhibited both greater retention of extinction and greater overall brain metabolic activity. Rats with higher retention of extinction also showed a relative increase in cytochrome oxidase activity in prefrontal cortical regions, especially anterior infralimbic cortex, dorsal and medial frontal cortex, and lateral orbital cortex. These regional metabolic increases were also correlated to the behavioral freezing index used to assess retention of extinction. It was concluded that MB administered postextinction could enhance retention of extinction memory through an increase in brain cytochrome oxidase activity.

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References
1.
Quirk G, Russo G, Barron J, Lebron K . The role of ventromedial prefrontal cortex in the recovery of extinguished fear. J Neurosci. 2000; 20(16):6225-31. PMC: 6772571. View

2.
LINDAHL P, Oberg K . The effect of rotenone on respiration and its point of attack. Exp Cell Res. 1961; 23:228-37. DOI: 10.1016/0014-4827(61)90033-7. View

3.
Berndt J, Callaway N, Gonzalez-Lima F . Effects of chronic sodium azide on brain and muscle cytochrome oxidase activity: a potential model to investigate environmental contributions to neurodegenerative diseases. J Toxicol Environ Health A. 2001; 63(1):67-77. DOI: 10.1080/152873901750128380. View

4.
Valla J, Berndt J, Gonzalez-Lima F . Energy hypometabolism in posterior cingulate cortex of Alzheimer's patients: superficial laminar cytochrome oxidase associated with disease duration. J Neurosci. 2001; 21(13):4923-30. PMC: 6762373. View

5.
Villarreal J, Gonzalez-Lima F, Berndt J . Water maze training in aged rats: effects on brain metabolic capacity and behavior. Brain Res. 2002; 939(1-2):43-51. DOI: 10.1016/s0006-8993(02)02545-3. View