Year: 2006
Type: dissertation
Abstract: The goal of this dissertation was to investigate the memory retention effects of \nmethylene blue (MB) in both appetitive and aversive memory tasks in rats. Methylene \nblue is a metabolic enhancer that improves memory retention in a variety of tasks \nincluding inhibitory avoidance, object recognition, spatial memory, and extinction of \nPavlovian fear conditioning. Low dose MB has no side effects on behavior. MB works \nas a metabolic enhancer by increasing brain cytochrome oxidase activity and oxygen \nconsumption. The first experiment was conducted to examine the effects of MB \ntreatment in normal rats in the hole board spatial memory task, to determine if it could \nenhance memory of discrimination learning of rewarded versus non-rewarded trials. \nSubjects treated with MB discriminated better between rewarded and non-rewarded trials \nas compared to control subjects, indicated by a greater number of correct responses on \nrewarded trials than non-rewarded trials. The second experiment was conducted to \ndetermine the effects of MB administered following acquisition trials in Pavlovian fear \nconditioning. Methylene blue-treated subjects demonstrated greater conditioned freezing \nto the tone conditioned stimulus (CS) without significant effects on context freezing. MB \nsubjects also had higher freezing scores following extinction, indicating that they retained \nstronger fear-conditioning than controls. The third experiment was conducted to \ncharacterize extinction in the congenitally helpless (CH) rat, an animal model of posttraumatic \nstress disorder and depression, and to determine if low dose MB could facilitate \nfear extinction memory in these subjects. CH rats exhibited abnormally high conditioned \nfreezing in response to the CS tone. They failed to show the gradual decrement in \nfreezing characteristic of the normal extinction curves seen in control subjects. \nAdministration of MB to CH rats significantly ameliorated their fear extinction deficit. It \nwas concluded that MB is a very promising treatment for memory enhancement, and if \nadministered post-training and in low doses, may be a potent memory-enhancing \ncompound with little to no side effects. MB provides an important therapeutic advantage \nbecause it optimizes neuronal energy metabolism during memory formation, while \navoiding side effects of drugs acting on synaptic transmission elsewhere in the brain.
Author: Kathryn M. Wrubel
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W2102431453