It is well documented that opiate and opioid peptide manipulations alter memory processes in young adult animals. In these investigations it has been consistently reported that post-training opiate antagonist administration enhances retention. The proposed research is aimed at investigating the role of opioid peptide function in memory processes in aged animals. The experiments are designed initially to examine whether age-related declines in learning/memory performance are sensitive to opiate treatments. Using spatial learning tasks which are sensitive to aging in rats, Part I of this proposal will examine the effects of post-training opiate antagonist treatments in young adult and aged rats on memory of spatial learning using the radial-arm maze. In Part II, experiments will be conducted to assess whether the medial septal area (MSA) is sensitive to the effects of opiate manipulations on spatial memory. Cholinergic neurons located in the MSA which project to the hippocampus have been demonstrated to be regulated by opiate receptor mechanisms. This cholinergic input to the hippocampus has been implicated in spatial learning in young animals and also appears to undergo an age-related functional decline which parallels the emergence of spatial learning deficits in rats. Finally, Part III of this proposal will examine whether treatments which alter the performance of young and aged animals on spatial learning tasks produce concomitant changes in place coding of neural units within the hippocampus. The results of this research will indicate whether the age-related decline in performance of spatial learning in old rats is (1) sensitive to treatments which improve memory for spatial learning in young animals; (2) sensitive to opiate manipulation at a brain site (MSA) which provides important input to the hippocampus; and (3) whether hippocampal neural correlates of the impaired spatial learning in old animals are altered by treatments which may improve maze performance. An understanding of the neural mechanisms underlying the effects of opiate manipulations on memory, particularly in aged animals, may have important clinical implications in light of recent reports that opiate antagonist administration benefits some patients with Alzheimer's disease.
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