Fudan Faifei Wong/Ma Lan team discovered neuronal clusters and loop mechanisms that cause negative emotions in morphine withdrawal

Recently, the research team of Feifei Wong/Ma Lan team from the Institute of Brain Science, Fudan University/State Key Laboratory of Medical Neurobiology, discovered that corticotropin releasing hormone (CRH) neurons in the central amygdala brain area and the ventral tegmental area (VTA) Inhibitory neural circuits between reward neurons activated by morphine mediate negative emotions caused by morphine withdrawal
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The research titled "CRHCeA→VTA inputsinhibit the positive ensembles to induce negative effect of opiate withdrawal" was published online in Molecular Psychiatry on October 12, 2021
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Morphine has a good analgesic effect and also brings a strong sense of euphoria (reward effect), but withdrawal after long-term use will induce withdrawal symptoms and negative emotions (negative reinforcement effect), leading to dependence or Addiction
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Studies have shown that morphine acts on the brain reward system to cause euphoria, and its withdrawal symptoms are mainly mediated by the down-regulation of the reward system and the activation of the stress-stress system
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The research team of Ma Lan and Fafei Wong used the cell labeling technology driven by immediate genes to mark the neuronal clusters in the VTA brain region activated by the initial morphine administration, and found that they are selectively connected to the nucleus accumbens neurons, mediated by a dopamine-dependent mechanism The rewarding effect of morphine
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After long-term administration of morphine, the inhibitory synaptic connections between the CRH neurons in the central amygdala and the morphine reward neuron clusters in the VTA are enhanced, leading to negative emotions such as disgust and anxiety
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Using pharmacology or gene editing technology to interfere with CRH receptors on the VTA morphine reward neuron cluster can block negative emotions such as anxiety
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This study reveals the negative feedback of the inhibitory loop to the reward system after the withdrawal of addictive drugs, which leads to the cellular mechanism of negative emotions, and provides new ideas for intervening with withdrawal emotional disorders and drug dependence
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Picture: CRHCeA→VTA inhibitory neural circuit acts on the GABAAR and CRHR1 receptors of Mor-reward neurons to mediate the negative emotional effect induced by morphine withdrawal Xiao and He Guanhong are the co-first authors of this article
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Professor Ma Lan from the Institute of Brain Science and Professor Feifei Wang from the School of Basic Medical Sciences are the co-corresponding authors
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The research was funded by the National Natural Science Foundation of China and the Shanghai Major Science and Technology Project
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Link to the paper: https:// Source: Fudan University Institute of Brain Science 2020 Hot Article Selection 1.
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