Methylene blue improves brain oxidative metabolism and memory retention in rats

Pharmacol Biochem Behav. 2004 Jan;77(1):175-81. doi: 10.1016/j.pbb.2003.10.007.


Methylene blue (MB) increases mitochondrial oxygen consumption and restores memory retention in rats metabolically impaired by inhibition of cytochrome c oxidase. This study tested two related hypotheses using biochemical and behavioral techniques: (1) that low-level MB would enhance brain cytochrome c oxidation, as tested in vitro in brain homogenates and after in vivo administration to rats and (2) that corresponding low-dose MB would enhance spatial memory retention in normal rats, as tested 24 h after rats were trained in a baited holeboard maze for 5 days with daily MB posttraining injections. The biochemical in vitro studies showed an increased rate of brain cytochrome c oxidation with the low but not the high MB concentrations tested. The in vivo administration studies showed that the corresponding MB low dose (1 mg/kg) increased brain cytochrome c oxidation 24 h after intraperitoneal injection, but not after 1 or 2 h postinjection. In the behavioral studies, spatial memory retention in probe trials (percentage of visits to training-baited holes compared to total visits) was significantly better for MB-treated than saline control groups (66% vs. 31%). Together the findings suggest that low-dose MB enhances spatial memory retention in normal rats by increasing brain cytochrome c oxidase activity.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Energy Metabolism / drug effects*
  • Energy Metabolism / physiology
  • Injections, Intraperitoneal
  • Male
  • Methylene Blue / administration & dosage
  • Methylene Blue / pharmacology*
  • Oxygen Consumption / drug effects*
  • Oxygen Consumption / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Retention, Psychology / drug effects*
  • Retention, Psychology / physiology


  • Methylene Blue