The major goal of this proposed research is to characterize the cellular mechanisms underlying the effects of endogenous opioid peptide-containing systems on learning and memory processes. The theoretical context underlying these studies is based on the suggestion that the neuronal mechanism of memory storage has two fundamental components, a centrally located memory trace and a peripherally located modulatory input. We suggest that opioid peptide systems are involved both in forming memory traces and in modulating associative strength. This research project has relevance to drug abuse because drug craving and compulsive drug-seeking behavior are aroused by memories of the reinforcing drug experience, and they may be maintained by plasticity in opioid peptide-containing neuronal systems. Experiments are proposed to assess the generality of the involvement of the endogenous opioid peptides, [Leu)- and [Met]enkephalin, in modulation of learning processes by characterizing their effects on acquisition and retention of appetitively-motivated conditioning. Studies also will investigate the opioid receptor subtype(s) through which these effects are mediated and the location of these receptor(s) vis-a-vis the blood-brain barrier. Additional experiments will investigate the opioid receptor- dependence of long-term potentiation, a candidate mechanism for memory storage processes, in several pathways within the hippocampus in vivo, using both acute studies in anesthetized animals and longer-term investigations in awake, freely moving animals with chronically implanted electrodes.
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