The primary long-range objective of this application is to elucidate and characterize the actions of endogenous opioid peptides in their role as neurotransmitters in the CNS. If the medical and societal problems related to opiate use and abuse are to be fully appreciated, our understanding of the normal, physiological actions of the endogenous opioid peptide system must be increased. More specifically, this proposal investigates the neurophysiological effects of the dynorphin family of opioid peptides in the hippocampal region of the brain. The relatively well characterized anatomy and physiology of the hippocampus makes it an ideal preparation in which to determine fundamental mechanisms by which endogenous opioid peptides may elicit their effects throughout the nervous system.
The specific aims address basic questions regarding the actions of dynorphin peptides, which are contained within granule cells of the dentate gyrus region in the hippocampal slice preparation: Under what conditions are these peptides released? What is the spatial extent of dynorphin influence on synaptic transmission in the molecular layer of the dentate gyrus? What is the mechanism involved in the release of these neurotransmitters from the dynorphin-containing granule cells? Electrophysiological techniques such as whole-cell voltage-clamp extracellular population responses, and dual intracellular recording methods will be applied in the in vitro hippocampal slice preparation to investigate these questions. It is expected that the information obtained from these studies will add to our understanding of how the nervous system normally utilizes endogenous opioids, and by extension, how it may respond under conditions of tolerance and/or addiction, where chronic opiate exposure has occurred.
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