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Nat Neurosci. 2019 Jul;22(7):1053-1056. doi: 10.1038/s41593-019-0421-4. Epub 2019 Jun 17.

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

Author information

1
The Department of Fundamental Neuroscience, The University of Lausanne, Lausanne, Switzerland.
2
Department of Physiology, The University of Bern, Bern, Switzerland.
3
Department of Basic Neuroscience, The University of Geneva, Geneva, Switzerland.
4
Department of Physiology, The University of Lausanne, Lausanne, Switzerland.
5
Inserm, UMR-S 839, Paris, France.
6
The Department of Fundamental Neuroscience, The University of Lausanne, Lausanne, Switzerland. manuel.mameli@unil.ch.
7
Inserm, UMR-S 839, Paris, France. manuel.mameli@unil.ch.

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.

PMID:
31209376
DOI:
10.1038/s41593-019-0421-4
[Indexed for MEDLINE]

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