Corticosteroid Sensitization Drives Opioid Addiction
Document Type
Article
Publication Date
3-16-2022
Publication Title
Molecular Psychiatry
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.
First Page
2492
Last Page
2501
PubMed ID
35296810
Volume
27
Issue
5
Recommended Citation
Carmack, Stephanie A.; Vendruscolo, Janaina C.M.; Adrienne McGinn, M.; Miranda-Barrientos, Jorge; Repunte-Canonigo, Vez; Bosse, Gabriel D.; Mercatelli, Daniele; Giorgi, Federico M.; Fu, Yu; Hinrich, Anthony J.; Jodelka, Francine M.; Ling, Karen; Messing, Robert O.; Peterson, Randall T.; Rigo, Frank; Edwards, Scott; Sanna, Pietro P.; Morales, Marisela; Hastings, Michelle L.; Koob, George F.; and Vendruscolo, Leandro F., "Corticosteroid Sensitization Drives Opioid Addiction" (2022). School of Medicine Faculty Publications. 1028.
https://digitalscholar.lsuhsc.edu/som_facpubs/1028