{"title":"Basal cortisol level modulates stress-induced opioid-seeking behavior","authors":"","doi":"10.1016/j.ynstr.2024.100684","DOIUrl":null,"url":null,"abstract":"<div><div>In preclinical studies and our human laboratory, the α<sub>2</sub>-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; <em>t</em> = 0 min) then hydrocortisone (0, 20, 40-mg; <em>t</em> = 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.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Stress","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2352289524000808","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal.
Basic, translational and clinical research on the following topics as they relate to stress will be covered:
Molecular substrates and cell signaling,
Genetics and epigenetics,
Stress circuitry,
Structural and physiological plasticity,
Developmental Aspects,
Laboratory models of stress,
Neuroinflammation and pathology,
Memory and Cognition,
Motivational Processes,
Fear and Anxiety,
Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse),
Neuropsychopharmacology.