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

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

doi:10.1038/s41593-019-0421-4

Scientific article

English

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

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

; Mameli, Manuel

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

Affiliation entities

Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

Research groups

Les dysfonctions synaptiques du cerveau (971)

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

Article (Published version)

Identifiers

PID : unige:126163
DOI : 10.1038/s41593-019-0421-4
PMID : 31209376

Journal ISSN1097-6256

567views

1downloads

Creation01/11/2019 11:00:00

First validation01/11/2019 11:00:00

Update13/10/2025 17:53:46

Status update15/03/2023 18:21:09

Last indexation03/11/2025 16:23:47

Archive ouverte UNIGE

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

Technical informations