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Papers of the Week

Papers: 15 Jun 2019 - 21 Jun 2019

Animal Studies, Pharmacology/Drug Development

2019 Jul

Nat Neurosci



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


Valentinova K, Tchenio A, Trusel M, Clerke JA, Lalive AL, Tzanoulinou S, Matera A, Moutkine I, Maroteaux L, Paolicelli RC, Volterra A, Bellone C, Mameli M
Nat Neurosci. 2019 Jul; 22(7):1053-1056.
PMID: 31209376.


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.