Memory facilitation by methylene blue: dose-dependent effect on behavior and brain oxygen consumption.

Methylene blue administered post-training improves memory retention in avoidance and appetitive tasks, and restores spatial memory impaired by an inhibitor of cytochrome oxidase. Methylene blue may improve memory retention by increasing brain oxygen utilization. We investigated which doses improve memory without nonspecific behavioral effects, and whether methylene blue enhances brain oxygen consumption. Different doses were evaluated 24 h after administration in wheel running, feeding, open field habituation and object recognition tests. The 1-10 mg/kg methylene blue-treated rats were not different from saline-treated rats in locomotion or feeding behavior. The 50-100 mg/kg doses decreased running wheel behavior. The 4 mg/kg dose improved behavioral habituation and object memory recognition. Dose-dependent effects of methylene blue on brain oxygen consumption revealed that low concentrations increased brain oxygen consumption in vitro and 24 h after in vivo administration. Therefore, methylene blue doses that increase brain oxygen consumption also facilitate memory retention.

[1]  F Gonzalez-Lima,et al.  Extinction memory improvement by the metabolic enhancer methylene blue. , 2004, Learning & memory.

[2]  D. Treit,et al.  Thigmotaxis as a test for anxiolytic activity in rats , 1988, Pharmacology Biochemistry and Behavior.

[3]  R. Bullock,et al.  Correlations between brain tissue oxygen tension, carbon dioxide tension, pH, and cerebral blood flow--a better way of monitoring the severely injured brain? , 1998, Surgical neurology.

[4]  G. Brown,et al.  Nitric oxide, cytochrome c and mitochondria. , 1999, Biochemical Society symposium.

[5]  J. Stucki,et al.  Inhibition and stimulation of long-chain fatty acid oxidation by chloroacetaldehyde and methylene blue in rats. , 1999, Journal of Pharmacology and Experimental Therapeutics.

[6]  A. Sadile,et al.  Behavioral habituation to spatial novelty: Interference and noninterference studies , 1994, Neuroscience & Biobehavioral Reviews.

[7]  B. Mayer,et al.  Novel actions of methylene blue. , 1993, European heart journal.

[8]  S. Bradberry.  Occupational Methaemoglobinaemia , 2003, Toxicological reviews.

[9]  B. Lauterburg,et al.  Pharmacokinetics and organ distribution of intravenous and oral methylene blue , 2000, European Journal of Clinical Pharmacology.

[10]  P. Molinoff,et al.  Basic Neurochemistry: Molecular, Cellular and Medical Aspects , 1989 .

[11]  David L. McCollum,et al.  Methylene blue restores spatial memory retention impaired by an inhibitor of cytochrome oxidase in rats , 2002, Neuroscience Letters.

[12]  K. Rajanna,et al.  Methylene Blue - Ascorbic Acid: An Undergraduate Experiment in Kinetics , 1997 .

[13]  Louis Sokoloff,et al.  Circulation and Energy Metabolism of the Brain , 1999 .

[14]  A. Shaw,et al.  Assessment of tissue oxygen tension: comparison of dynamic fluorescence quenching and polarographic electrode technique , 2002, Critical care.

[15]  J. Delacour,et al.  A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data , 1988, Behavioural Brain Research.

[16]  C. Messier.  Glucose improvement of memory: a review. , 2004, European journal of pharmacology.

[17]  F. Gonzalez-Lima,et al.  Methylene blue improves brain oxidative metabolism and memory retention in rats , 2004, Pharmacology Biochemistry and Behavior.

[18]  Sarah E. Mowry,et al.  Kinetics of Methylene Blue Reduction by Ascorbic Acid , 1999 .

[19]  B. Hyman,et al.  Do defecs in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? , 1993, Trends in Neurosciences.

[20]  D. Diamond,et al.  Cytochrome Oxidase Inhibition: A Novel Animal Model of Alzheimer's Disease , 1992, Journal of geriatric psychiatry and neurology.

[21]  J. Stucki,et al.  Stimulation of respiration by methylene blue in rat liver mitochondria , 1997, FEBS letters.

[22]  P. Lestage,et al.  Effects of S 18986-1, a novel cognitive enhancer, on memory performances in an object recognition task in rats. , 2000, European journal of pharmacology.

[23]  F. Gonzalez-Lima,et al.  Effects of Chronic Sodium Azide on Brain and Muscle Cytochrome Oxidase Activity: A Potential Model to Investigate Environmental Contributions to Neurodegenerative Diseases , 2001, Journal of toxicology and environmental health. Part A.

[24]  F. Gonzalez-Lima.  Cytochrome Oxidase in Neuronal Metabolism and Alzheimer’s Disease , 2013, Springer US.

[25]  James L. McGaugh,et al.  Methylene blue alters retention of inhibitory avoidance responses , 1978 .

[26]  F Gonzalez-Lima,et al.  Energy Hypometabolism in Posterior Cingulate Cortex of Alzheimer's Patients: Superficial Laminar Cytochrome Oxidase Associated with Disease Duration , 2001, The Journal of Neuroscience.

[27]  A Scott,et al.  Support of thyroxine-induced swelling of liver mitochondria by generation of high energy intermediates at any one of three sites in electron transport. , 1966, The Journal of biological chemistry.

[28]  J. C. Torre.  Alzheimer's disease is a vasocognopathy: a new term to describe its nature. , 2004 .

[29]  P E LINDAHL,et al.  The effect of rotenone on respiration and its point of attack. , 1961, Experimental cell research.

[30]  C. Cooper,et al.  Mitochondria and Cell Death , 2000 .

[31]  R. Sutherland,et al.  Reduced cytochrome oxidase and memory dysfunction after chronic brain ischemia in aged rats , 1997, Neuroscience Letters.

[32]  T. Cerny,et al.  Methylene blue and the neurotoxic mechanisms of ifosfamide encephalopathy , 1996, European Journal of Clinical Pharmacology.

[33]  Seong-Gi Kim,et al.  Effect of hyperoxia, hypercapnia, and hypoxia on cerebral interstitial oxygen tension and cerebral blood flow , 2001, Magnetic resonance in medicine.

[34]  C. Dawson,et al.  Pulmonary endothelial thiazine uptake: separation of cell surface reduction from intracellular reoxidation. , 1997, The American journal of physiology.

[35]  F. Gonzalez-Lima,et al.  Regional brain effects of sodium azide treatment on cytochrome oxidase activity: a quantitative histochemical study , 1995, Metabolic Brain Disease.

[36]  G. Naylor,et al.  A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manicdepressive psychosis , 1986, Biological Psychiatry.

[37]  F. Gonzalez-Lima,et al.  Quantitative Histochemistry of Cytochrome Oxidase Activity , 1998 .