This ADAMHA RSDA renewal application (Level II) will support an investigator working on the neurobiological basis of learning and memory. This research program focuses on neurochemical regulation of these functions in limbic system structures. One major goal of this work is to examine the organization of limbic opioid peptides and their relation to other systems that innervate the forebrain (ascending norepinephrine pathways and the basal forebrain cholinergic (ACh) system). In a series of experiments a special emphasis is placed on assessing opioid peptide regulation of the septo-hippocampal ACh pathway (PART II). In this context complementary experiments are also designed to assess the effects of aging on both behavior and the function of these neurochemical systems, i.e. ACh and opioid peptide (PART IV). A second major theme of this work is to determine the principles that govern the activity of opioid peptides. Behavioral experiments (PART I) are designed to further analyze the training conditions that exhibit sensitivity to opiate antagonist treatments. Using classical conditioning procedures (overshadowing and conditioned inhibition) these experiments are designed to make contact with research linking opioid peptide function to mechanisms of attention. In PART III the effects of selected training procedures on opioid peptide content/activity in limbic structures (amygdala and hippocampus) will be examined. The goals of this program are to provide information about the neurochemical systems that underly normal learning and memory processes and to provide a basis for the development of treatment strategies for clinical conditions characterized by a deterioration in these capacities. Further plans for collaboration and extended training with other neuroscientists at the applicant's institution and at NIEHS (National Institute of Environmental Health Sciences), and a proposed visit to another major laboratory are included in the application.
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