MOP Receptor Effects on the Hippocampal CA1 Network

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DESCRIPTION (provided by applicant): The high rate of relapse in opioid drug users is often triggered by the exposure to environmental cues associated with previous drug use. These associations are thought to involve the activation of mu-opioid peptide (MOP) receptors within the hippocampus. MOP receptor activation on GABAergic inhibitory interneurons within the hippocampus inhibits the release of GABA onto pyramidal cells, which can profoundly affect hippocampal network function and modulate the flow of information to other areas of the CNS. It is this change in hippocampal network function that may be involved in the formation of the associations made between environmental cues and chronic drug abuse. Although it is known that MOP receptor activation inhibits GABAergic synaptic transmission, the precise interneurons inhibited by MOP receptor activation and their specific effect on hippocampal CA1 network function is not completely understood. Based on preliminary studies, we hypothesize that MOP receptors inhibit the release of GABA from interneurons that innervate the entire somatic and dendritic extent of CA1 pyramidal cells. Furthermore, we suggest that MOP receptor activation augments excitatory inputs, facilitates the propagation of excitatory information between pyramidal cell compartments, and facilitates the temporal and spatial integration of excitatory activity within the CA1 network. The effects of MOP receptors on hippocampal CA1 network function will be examined using voltage-sensitive dye (VSD) imaging from rat brain slices. VSD imaging will allow us to simultaneously measure both excitatory and inhibitory activity throughout the entire neural network of hippocampal CA1 brain slices with high spatial and temporal resolution. These studies will provide a foundation to address the long-term goals of how chronic opioid use alters MOP receptor and neural network function. The results from these studies will provide important information regarding MOP receptor-induced changes in network activity and may possibly lead to the development of treatments for opioid addiction.