Signaling mechanisms of μ-opioid receptor (MOR) in the hippocampus: disinhibition versus astrocytic glutamate regulation
- 15 July 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Cellular and Molecular Life Sciences
- Vol. 78 (2), 415-426
- https://doi.org/10.1007/s00018-020-03595-8
Abstract
μ-opioid receptor (MOR) is a class of opioid receptors that is critical for analgesia, reward, and euphoria. MOR is distributed in various brain regions, including the hippocampus, where traditionally, it is believed to be localized mainly at the presynaptic terminals of the GABAergic inhibitory interneurons to exert a strong disinhibitory effect on excitatory pyramidal neurons. However, recent intensive research has uncovered the existence of MOR in hippocampal astrocytes, shedding light on how astrocytic MOR participates in opioid signaling via glia-neuron interaction in the hippocampus. Activation of astrocytic MOR has shown to cause glutamate release from hippocampal astrocytes and increase the excitability of presynaptic axon fibers to enhance the release of glutamate at the Schaffer Collateral-CA1 synapses, thereby, intensifying the synaptic strength and plasticity. This novel mechanism involving astrocytic MOR has been shown to participate in hippocampus-dependent conditioned place preference. Furthermore, the signaling of hippocampal MOR, whose action is sexually dimorphic, is engaged in adult neurogenesis, seizure, and stress-induced memory impairment. In this review, we focus on the two profoundly different hippocampal opioid signaling pathways through either GABAergic interneuronal or astrocytic MOR. We further compare and contrast their molecular and cellular mechanisms and their possible roles in opioid-associated conditioned place preference and other hippocampus-dependent behaviors.Keywords
Funding Information
- Institute for Basic Science (IBS-R001-D2)
This publication has 107 references indexed in Scilit:
- TREK-1 and Best1 Channels Mediate Fast and Slow Glutamate Release in Astrocytes upon GPCR ActivationCell, 2012
- Crystal structure of the µ-opioid receptor bound to a morphinan antagonistNature, 2012
- The Influences of Reproductive Status and Acute Stress on the Levels of Phosphorylated Mu Opioid Receptor Immunoreactivity in Rat HippocampusFrontiers in Endocrinology, 2011
- Ovarian steroids alter mu opioid receptor trafficking in hippocampal parvalbumin GABAergic interneuronsExperimental Neurology, 2009
- Effect of chronic morphine on the dentate gyrus neurogenic microenvironmentNeuroscience, 2009
- Time course of morphine's effects on adult hippocampal subgranular zone reveals preferential inhibition of cells in S phase of the cell cycle and a subpopulation of immature neuronsNeuroscience, 2008
- Ovarian steroids modulate leu-enkephalin levels and target leu-enkephalinergic profiles in the female hippocampal mossy fiber pathwayBrain Research, 2008
- Layer selective presynaptic modulation of excitatory inputs to hippocampal cornu Ammon 1 by μ-opioid receptor activationNeuroscience, 2008
- Hippocampal long-term depression mediates acute stress-induced spatial memory retrieval impairmentProceedings of the National Academy of Sciences of the United States of America, 2007
- Knockout of the mu opioid receptor enhances the survival of adult-generated hippocampal granule cell neuronsNeuroscience, 2007