Morphine withdrawal recruits lateral habenula cytokine signaling to reduce synaptic excitation and sociability.
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
Social Behavior
Substance Withdrawal Syndrome
/ physiopathology
Synaptic Transmission
/ physiology
Tumor Necrosis Factor-alpha
/ physiology
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
18
10
2018
accepted:
07
05
2019
pubmed:
19
6
2019
medline:
19
7
2019
entrez:
19
6
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31209376
doi: 10.1038/s41593-019-0421-4
pii: 10.1038/s41593-019-0421-4
doi:
Substances chimiques
Cytokines
0
Receptors, Glutamate
0
Receptors, N-Methyl-D-Aspartate
0
Receptors, Tumor Necrosis Factor, Type I
0
Tnfrsf1a protein, mouse
0
Tumor Necrosis Factor-alpha
0
Naloxone
36B82AMQ7N
Morphine
76I7G6D29C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM