PUBLICATION
Corticosteroid sensitization drives opioid addiction
- Authors
- Carmack, S.A., Vendruscolo, J.C.M., Adrienne McGinn, M., Miranda-Barrientos, J., Repunte-Canonigo, V., Bosse, G.D., Mercatelli, D., Giorgi, F.M., Fu, Y., Hinrich, A.J., Jodelka, F.M., Ling, K., Messing, R.O., Peterson, R.T., Rigo, F., Edwards, S., Sanna, P.P., Morales, M., Hastings, M.L., Koob, G.F., Vendruscolo, L.F.
- ID
- ZDB-PUB-220318-9
- Date
- 2022
- Source
- Molecular psychiatry 27(5): 2492-2501 (Journal)
- Registered Authors
- Bosse, Gabriel, Peterson, Randall
- Keywords
- none
- MeSH Terms
-
- Adrenal Cortex Hormones
- Animals
- Corticotropin-Releasing Hormone
- Opioid-Related Disorders*
- Rats
- Substance Withdrawal Syndrome*
- Zebrafish
- PubMed
- 35296810 Full text @ Mol. Psychiatry
Citation
Carmack, S.A., Vendruscolo, J.C.M., Adrienne McGinn, M., Miranda-Barrientos, J., Repunte-Canonigo, V., Bosse, G.D., Mercatelli, D., Giorgi, F.M., Fu, Y., Hinrich, A.J., Jodelka, F.M., Ling, K., Messing, R.O., Peterson, R.T., Rigo, F., Edwards, S., Sanna, P.P., Morales, M., Hastings, M.L., Koob, G.F., Vendruscolo, L.F. (2022) Corticosteroid sensitization drives opioid addiction. Molecular psychiatry. 27(5):2492-2501.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping