Basal cortisol level modulates stress-induced opioid-seeking behavior.

Area of Science:

• Neuroscience
• Psychopharmacology
• Addiction Medicine

Background:

• Yohimbine, an α2-noradrenergic antagonist, promotes drug-seeking behavior.
• Glucocorticoid receptor agonists like hydrocortisone also influence stress and reward pathways.
• Understanding the combined effects of these systems is crucial for addiction treatment.

Purpose of the Study:

• To evaluate the dose-dependent effects of yohimbine and hydrocortisone, alone and in combination, on stress-reactivity and opioid-seeking.
• To model the intensity-dependent stimulation of noradrenergic and glucocorticoid systems.
• To investigate the role of basal cortisol levels in modulating these effects.

Main Methods:

• A double-blind, placebo-controlled, within-subject study with 12 participants diagnosed with opioid use disorder (OUD) stabilized on buprenorphine.
• Administration of varying oral doses of yohimbine (0, 27, 54 mg) and hydrocortisone (0, 20, 40 mg) in a 3x3 factorial design.
• Assessment of subjective effects, cardiovascular responses, salivary cortisol and α-amylase, and a progressive ratio task for opioid vs. money reinforcement.

Main Results:

• Yohimbine increased blood pressure, α-amylase, and anxiety, while decreasing opioid withdrawal symptoms.
• Hydrocortisone increased cortisol levels.
• Combined yohimbine and hydrocortisone shifted responding towards opioid-seeking in participants with lower baseline cortisol.

Conclusions:

• Noradrenergic and glucocorticoid system stimulation potentiates opioid-seeking behavior, particularly in individuals with lower baseline cortisol.
• Basal HPA-axis activity and acute stressors can increase the relative reinforcing efficacy of opioids in individuals with OUD on buprenorphine.
• These findings highlight potential limitations of current OUD treatments and suggest novel intervention targets to mitigate stress-induced opioid-seeking.