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

Kristina Valentinova, Anna Tchenio, Massimo Trusel, Joseph A. Clerke, Arnaud L. Lalive, Stamatina Tzanoulinou, Alessandro Matera, Imane Moutkine, Luc Maroteaux, Rosa C. Paolicelli, Andrea Volterra, Camilla Bellone, Manuel Mameli

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1053-1056
Number of pages4
JournalNature neuroscience
Volume22
Issue number7
DOIs
StatePublished - Jul 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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