Corticosteroid sensitization drives opioid addiction.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
19
06
2021
accepted:
22
02
2022
revised:
02
02
2022
pubmed:
18
3
2022
medline:
31
5
2022
entrez:
17
3
2022
Statut:
ppublish
Résumé
The global crisis of opioid overdose fatalities has led to an urgent search to discover the neurobiological mechanisms of opioid use disorder (OUD). A driving force for OUD is the dysphoric and emotionally painful state (hyperkatifeia) that is produced during acute and protracted opioid withdrawal. Here, we explored a mechanistic role for extrahypothalamic stress systems in driving opioid addiction. We found that glucocorticoid receptor (GR) antagonism with mifepristone reduced opioid addiction-like behaviors in rats and zebrafish of both sexes and decreased the firing of corticotropin-releasing factor neurons in the rat amygdala (i.e., a marker of brain stress system activation). In support of the hypothesized role of glucocorticoid transcriptional regulation of extrahypothalamic GRs in addiction-like behavior, an intra-amygdala infusion of an antisense oligonucleotide that blocked GR transcriptional activity reduced addiction-like behaviors. Finally, we identified transcriptional adaptations of GR signaling in the amygdala of humans with OUD. Thus, GRs, their coregulators, and downstream systems may represent viable therapeutic targets to treat the "stress side" of OUD.
Identifiants
pubmed: 35296810
doi: 10.1038/s41380-022-01501-1
pii: 10.1038/s41380-022-01501-1
pmc: PMC10406162
mid: NIHMS1916420
doi:
Substances chimiques
Adrenal Cortex Hormones
0
Corticotropin-Releasing Hormone
9015-71-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2492-2501Subventions
Organisme : NIDA NIH HHS
ID : R01 DA043268
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DA000644
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA048882
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DA000605
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026075
Pays : United States
Informations de copyright
© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
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