Methylene blue improves brain oxidative metabolism and memory retention in rats.
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.
Callaway
Narriman Lee
NL
Departments of Psychology, Neuroscience, and Pharmacology, University of Texas at Austin, 1 University Station A8000, Austin, TX 78712, USA.
Riha
Penny D
PD
Bruchey
Aleksandra K
AK
Munshi
Zeenat
Z
Gonzalez-Lima
F
F
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D007274:Injections, Intraperitoneal; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012153:Retention, Psychology / Q000187:drug effects* / Q000502:physiology
D008751:Methylene Blue