Oxycodone withdrawal induces HDAC1/HDAC2-dependent transcriptional maladaptations in the reward pathway in a mouse model of peripheral nerve injury.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
received:
27
09
2021
accepted:
25
04
2023
medline:
7
7
2023
pubmed:
9
6
2023
entrez:
8
6
2023
Statut:
ppublish
Résumé
The development of physical dependence and addiction disorders due to misuse of opioid analgesics is a major concern with pain therapeutics. We developed a mouse model of oxycodone exposure and subsequent withdrawal in the presence or absence of chronic neuropathic pain. Oxycodone withdrawal alone triggered robust gene expression adaptations in the nucleus accumbens, medial prefrontal cortex and ventral tegmental area, with numerous genes and pathways selectively affected by oxycodone withdrawal in mice with peripheral nerve injury. Pathway analysis predicted that histone deacetylase (HDAC) 1 is a top upstream regulator in opioid withdrawal in nucleus accumbens and medial prefrontal cortex. The novel HDAC1/HDAC2 inhibitor, Regenacy Brain Class I HDAC Inhibitor (RBC1HI), attenuated behavioral manifestations of oxycodone withdrawal, especially in mice with neuropathic pain. These findings suggest that inhibition of HDAC1/HDAC2 may provide an avenue for patients with chronic pain who are dependent on opioids to transition to non-opioid analgesics.
Identifiants
pubmed: 37291337
doi: 10.1038/s41593-023-01350-3
pii: 10.1038/s41593-023-01350-3
doi:
Substances chimiques
Oxycodone
CD35PMG570
Narcotics
0
Histone Deacetylase 1
EC 3.5.1.98
Analgesics, Opioid
0
Histone Deacetylase 2
EC 3.5.1.98
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1229-1244Subventions
Organisme : NINDS NIH HHS
ID : R01 NS086444
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS111351
Pays : United States
Organisme : NIDA NIH HHS
ID : P01 DA047233
Pays : United States
Organisme : NIDA NIH HHS
ID : T32 DA007135
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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