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Scientific article
English

Morphine withdrawal recruits lateral habenula cytokine signaling to reduce synaptic excitation and sociability

Published inNature Neuroscience, vol. 22, no. 7, p. 1053-1056
Publication date2019
Abstract

The lateral habenula encodes aversive stimuli contributing to negative emotional states during drug withdrawal. Here we report that morphine withdrawal in mice leads to microglia adaptations and diminishes glutamatergic transmission onto raphe-projecting lateral habenula neurons. Chemogenetic inhibition of this circuit promotes morphine withdrawal-like social deficits. Morphine withdrawal-driven synaptic plasticity and reduced sociability require tumor necrosis factor-α (TNF-α) release and neuronal TNF receptor 1 activation. Hence, habenular cytokines control synaptic and behavioral adaptations during drug withdrawal.

Keywords
  • Adaptation
  • Psychological
  • Animals
  • Cytokines/physiology
  • Female
  • Habenula/physiology
  • Male
  • Mice
  • Mice
  • Inbred C57BL
  • Microglia/physiology
  • Morphine/adverse effects
  • Naloxone/toxicity
  • Neuronal Plasticity
  • Random Allocation
  • Receptors
  • Glutamate/analysis
  • Receptors
  • N-Methyl-D-Aspartate/analysis
  • Receptors
  • Tumor Necrosis Factor
  • Type I/genetics/physiology
  • Social Behavior
  • Substance Withdrawal Syndrome/physiopathology/psychology
  • Synaptic Transmission/physiology
  • Tumor Necrosis Factor-alpha/physiology
Citation (ISO format)
VALENTINOVA, Kristina et al. Morphine withdrawal recruits lateral habenula cytokine signaling to reduce synaptic excitation and sociability. In: Nature Neuroscience, 2019, vol. 22, n° 7, p. 1053–1056. doi: 10.1038/s41593-019-0421-4
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Article (Published version)
accessLevelRestricted
Identifiers
ISSN of the journal1097-6256
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Creation11/01/2019 11:00:00 AM
First validation11/01/2019 11:00:00 AM
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