Endogenous Opioid Regulation of Hippocampal Function

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This chapter discusses the anatomy and physiology of opioids in the hippocampus. It also discusses the roles of opioids in learning and memory processes and epileptogenesis. Endogenous opioid peptides modulate neural transmission in the hippocampus. Proenkephalin-derived peptides have been demonstrated to act at mu and delta opioid receptors to inhibit GABA release from inhibitory interneurons, resulting in the increased excitability of hippocampal pyramidal cells and dentate gyrus granule cells. Prodynorphin-derived peptides primarily act at presynaptic kappa opioid receptors to inhibit excitatory amino acid release from perforant path and mossy fiber terminals. Opioid receptors reduce membrane excitability by modulating ion conductances; and in this way, they may decrease voltage-dependent calcium influx and transmitter release. Synaptic plasticity in the hippocampus also is modulated by endogenous opioids. Enkephalins facilitate long-term potentiation, whereas dynorphins inhibit the induction of this type of neuroplasticity. Opioids may play important roles in hippocampal epilepsy. Recurrent seizures induce changes in the expression of opioid peptides and receptors. Also, enkephalins have proconvulsant effects in the epileptic hippocampus, whereas dynorphins may function as endogenous anticonvulsants.

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