Interaction Of Non-opioid Peptides With Opioid Receptors

National Institute On Drug Abuse

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Abstract

The hipocampus is a brain area known to be involved in learning and memory in both humans and animals. In addition, the activation of opioid receptors in the hippocampus can disrupt memory formation, and synchronous neural processes. Several studies to date have provided evidence that non-opioid peptides, such as cholecystokinin (CCK), can disrupt opioid-mediated processes, including analgesia. Therefore, we have begun studies to evaluate the hypothesis that the actions of CCK on opioid-mediated effects is due to a form of heterologous desensitization of the mu opioid receptor following activation of CCK-B receptors. These studies are conducted in the rodent brain slice preparation using whole-cell electrophysiological techniques. Studies completed to date indicate that activation of mu opioid or CCK-B receptors on hippocampal GABAergic interneurons demonstrate opposite effects on membrane potential and cellular excitability, such that CCK-B receptors excite, and mu opioid inhibit interneuron activity. Studies to be completed in the following year will determine whether preceding activation of CCK-B receptors diminishes subsequent responses by interneurons to morphine. If this is indeed the case then we will pursue the hypothesis that activation of CCK-B receptors alters opioid receptor signaling via biochemical alterations in the mu opioid receptor.