Basal cortisol level modulates stress-induced opioid-seeking behavior
In preclinical studies and our human laboratory, the α2-noradrenergic autoreceptor antagonist yohimbine was found to promote drug-seeking behavior. This study evaluated effects of dose-combinations of yohimbine and the glucocorticoid receptor agonist hydrocortisone to model intensity-dependent effec...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-11-01
|
| Series: | Neurobiology of Stress |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352289524000808 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850065550020968448 |
|---|---|
| author | Mark K. Greenwald Eric A. Woodcock Tabitha E.H. Moses Leslie H. Lundahl |
| author_facet | Mark K. Greenwald Eric A. Woodcock Tabitha E.H. Moses Leslie H. Lundahl |
| author_sort | Mark K. Greenwald |
| collection | DOAJ |
| description | In preclinical studies and our human laboratory, the α2-noradrenergic autoreceptor antagonist yohimbine was found to promote drug-seeking behavior. This study evaluated effects of dose-combinations of yohimbine and the glucocorticoid receptor agonist hydrocortisone to model intensity-dependent effects of stimulating each neurochemical system, alone and together, on stress-reactivity and opioid-seeking. Twelve regular heroin-using participants diagnosed with opioid use disorder (OUD) were stabilized on sublingual buprenorphine (8-mg/day), then passed a hydromorphone 18-mg vs. placebo intramuscular reinforcement screen. Across 9 experimental conditions (3 × 3 within-subject, randomized crossover, placebo-controlled, double-blind design) during inpatient buprenorphine maintenance, combinations of oral pretreatment doses of yohimbine (0, 27, 54-mg; t = 0 min) then hydrocortisone (0, 20, 40-mg; t = 45 min) were administered. In each condition, subjective drug and mood effects, cardiovascular responses, and saliva cortisol and α-amylase levels were assessed to evaluate stress-reactivity, and participants completed a 12-trial choice progressive ratio task during which they could earn units of hydromorphone (1.5-mg intramuscular) and/or money ($2.00). Yohimbine dose-dependently increased blood pressure, α-amylase, and anxiety scores, and decreased opioid agonist symptoms; hydrocortisone dose-dependently increased cortisol levels. Yohimbine/hydrocortisone dose-combinations significantly shifted within-session responding from money to opioid-seeking among participants with lower basal cortisol levels. These findings replicate yohimbine effects on stress biomarkers and demonstrate that noradrenergic/glucocorticoid-potentiated opioid-seeking is modulated by basal cortisol level. In persons with OUD stabilized on buprenorphine, basal HPA-axis activity and acute stressors can enhance opioid relative reinforcing efficacy. These factors may limit OUD treatment efficacy and highlight the need for novel interventions that prevent stress-induced opioid-seeking. |
| format | Article |
| id | doaj-art-7e8ce656a1ae49f99c1135d30ec35764 |
| institution | DOAJ |
| issn | 2352-2895 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Stress |
| spelling | doaj-art-7e8ce656a1ae49f99c1135d30ec357642025-08-20T02:48:58ZengElsevierNeurobiology of Stress2352-28952024-11-013310068410.1016/j.ynstr.2024.100684Basal cortisol level modulates stress-induced opioid-seeking behaviorMark K. Greenwald0Eric A. Woodcock1Tabitha E.H. Moses2Leslie H. Lundahl3Dept. of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USA; Dept. of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USA; Corresponding author. Substance Addiction Research Division, Department of Psychiatry and Behavioral Neurosciences, 3901 Chrysler Service Drive, Suite 2A, Detroit, MI, 48201, USA.Dept. of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USA; Dept. of Pharmacology, School of Medicine, Wayne State University, Detroit, MI, USADept. of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USADept. of Psychiatry and Behavioral Neurosciences, School of Medicine, Wayne State University, Detroit, MI, USAIn preclinical studies and our human laboratory, the α2-noradrenergic autoreceptor antagonist yohimbine was found to promote drug-seeking behavior. This study evaluated effects of dose-combinations of yohimbine and the glucocorticoid receptor agonist hydrocortisone to model intensity-dependent effects of stimulating each neurochemical system, alone and together, on stress-reactivity and opioid-seeking. Twelve regular heroin-using participants diagnosed with opioid use disorder (OUD) were stabilized on sublingual buprenorphine (8-mg/day), then passed a hydromorphone 18-mg vs. placebo intramuscular reinforcement screen. Across 9 experimental conditions (3 × 3 within-subject, randomized crossover, placebo-controlled, double-blind design) during inpatient buprenorphine maintenance, combinations of oral pretreatment doses of yohimbine (0, 27, 54-mg; t = 0 min) then hydrocortisone (0, 20, 40-mg; t = 45 min) were administered. In each condition, subjective drug and mood effects, cardiovascular responses, and saliva cortisol and α-amylase levels were assessed to evaluate stress-reactivity, and participants completed a 12-trial choice progressive ratio task during which they could earn units of hydromorphone (1.5-mg intramuscular) and/or money ($2.00). Yohimbine dose-dependently increased blood pressure, α-amylase, and anxiety scores, and decreased opioid agonist symptoms; hydrocortisone dose-dependently increased cortisol levels. Yohimbine/hydrocortisone dose-combinations significantly shifted within-session responding from money to opioid-seeking among participants with lower basal cortisol levels. These findings replicate yohimbine effects on stress biomarkers and demonstrate that noradrenergic/glucocorticoid-potentiated opioid-seeking is modulated by basal cortisol level. In persons with OUD stabilized on buprenorphine, basal HPA-axis activity and acute stressors can enhance opioid relative reinforcing efficacy. These factors may limit OUD treatment efficacy and highlight the need for novel interventions that prevent stress-induced opioid-seeking.http://www.sciencedirect.com/science/article/pii/S2352289524000808StressOpioid seekingNoradrenergicGlucocorticoidCortisol |
| spellingShingle | Mark K. Greenwald Eric A. Woodcock Tabitha E.H. Moses Leslie H. Lundahl Basal cortisol level modulates stress-induced opioid-seeking behavior Neurobiology of Stress Stress Opioid seeking Noradrenergic Glucocorticoid Cortisol |
| title | Basal cortisol level modulates stress-induced opioid-seeking behavior |
| title_full | Basal cortisol level modulates stress-induced opioid-seeking behavior |
| title_fullStr | Basal cortisol level modulates stress-induced opioid-seeking behavior |
| title_full_unstemmed | Basal cortisol level modulates stress-induced opioid-seeking behavior |
| title_short | Basal cortisol level modulates stress-induced opioid-seeking behavior |
| title_sort | basal cortisol level modulates stress induced opioid seeking behavior |
| topic | Stress Opioid seeking Noradrenergic Glucocorticoid Cortisol |
| url | http://www.sciencedirect.com/science/article/pii/S2352289524000808 |
| work_keys_str_mv | AT markkgreenwald basalcortisollevelmodulatesstressinducedopioidseekingbehavior AT ericawoodcock basalcortisollevelmodulatesstressinducedopioidseekingbehavior AT tabithaehmoses basalcortisollevelmodulatesstressinducedopioidseekingbehavior AT lesliehlundahl basalcortisollevelmodulatesstressinducedopioidseekingbehavior |