Administration of glucose enhances learning and memory in rodents and humans, and is especially effective in reversing age-related impairments in memory. This research project will examine whether age-related changes in the regulation of blood and brain glucose contribute to age-related impairments of learning and memory. Training is often accompanied by increases in circulating epinephrine levels, with subsequent increases in circulating glucose levels, in a manner related to endogenous modulation of learning and memory. Recent evidence suggests that, in aged male Fischer 344 rats, there is an uncoupling between epinephrine release from the adrenal medulla and subsequent increases in blood glucose levels, resulting in diminished responses of circulating glucose levels to training. The reduced responses of blood glucose levels may significantly influence brain processes important for learning and memory. In the brain, extracellular glucose levels in the hippocampus are depleted while rats are tested on a hippocampus dependent spontaneous alternation task. As compared to young adult rats, aged rats perform poorly on this task and exhibit exaggerated depletion of glucose in the hippocampus during behavioral testing. Injections (i.p.) of glucose block the depletion in the hippocampus and also enhance performance on the alternation task in aged rats. Together, these findings suggest that altered control of glucose levels in blood and brain during aging may contribute to age-related impairments of memory. Using young and old rats, the proposed experiments will examine the contribution of age-related changes in responses of glucose to training to age-related changes in learning and memory. Proposed experiments will examine changes in circulating and brain glucose responses to training in aged rats, assessing the relationship of these changes to learning and memory. The experiments will determine whether the depletion of extracellular glucose levels in the hippocampus, prominent in aged rats, is evident also in the striatum and prefrontal cortex. These experiments include measures of changes in extracellular brain glucose levels during training with and without treatments that enhance learning and memory in aged rats and also assess the efficacy in enhancing learning and memory of microinjections of glucose directly into those brain areas in which glucose is depleted by training.
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