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Published on: February 18, 2016
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Corticosteroid sensitization drives opioid addiction
Stephanie A Carmack1,2, Janaina C M Vendruscolo1, M Adrienne McGinn1
1Integrative Neuroscience Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institute of Health, Baltimore, MD, USA.
Molecular Psychiatry
|March 17, 2022
Summary
Glucocorticoid receptors (GRs) in the brain
Area of Science:
- Neurobiology
- Addiction research
- Pharmacology
Background:
- Opioid use disorder (OUD) is a global crisis driven by withdrawal-induced hyperkatifeia.
- Understanding the neurobiological underpinnings of OUD is critical for developing effective treatments.
Purpose of the Study:
- To investigate the role of extrahypothalamic stress systems in opioid addiction.
- To explore glucocorticoid receptor (GR) signaling in the amygdala as a potential therapeutic target for OUD.
Main Methods:
- Administered mifepristone (a GR antagonist) to rats and zebrafish to assess addiction-like behaviors.
- Measured corticotropin-releasing factor (CRF) neuron activity in the rat amygdala.
- Used antisense oligonucleotides to block GR transcriptional activity in the rat amygdala.
- Analyzed GR signaling pathways in post-mortem human brain samples from individuals with OUD.
Main Results:
- Mifepristone significantly reduced opioid addiction-like behaviors in both species.
- GR antagonism decreased CRF neuron firing in the rat amygdala, indicating reduced stress system activation.
- Blocking GR transcriptional activity in the amygdala also reduced addiction-like behaviors.
- Transcriptional adaptations in GR signaling were identified in the amygdala of humans with OUD.
Conclusions:
- Glucocorticoid receptor (GR) signaling in extrahypothalamic stress systems, particularly the amygdala, plays a mechanistic role in driving opioid addiction.
- Targeting GRs and their associated pathways offers a promising therapeutic strategy to address the "stress side" of opioid use disorder.
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