title: Naloxone-induced cortisol predicts mu opioid receptor binding potential in specific brain regions of healthy subjects.
abstract: Investigators have administered the opioid receptor antagonist, naloxone, to interrogate the hypothalamic-pituitary-adrenal (HPA) axis response under the assumption that this technique provides a measure of endogenous opioid activity. However it has never been tested whether provocation of the HPA axis with naloxone provides a surrogate marker for direct measurement of endogenous opioid activity using PET imaging as the gold standard. To test this hypothesis, eighteen healthy subjects underwent a PET scan with the mu-opioid receptor (MOR) selective ligand [(11)C]carfentanil (CFN). The following day ACTH and cortisol responses were assessed using a technique which allows administration of 5 incremental doses of naloxone (0, 25, 50, 100 and 250μg/kg) in a single session. Relationships between ACTH and cortisol responses and [(11)C]CFN binding potential (BP(ND)) were examined in 5 brain regions involved in the regulation of the HPA axis and/or regions with high concentrations of MOR. All subjects mounted graded ACTH and cortisol responses to naloxone administrations. There were significant negative relationships between cortisol response to naloxone and [(11)C]CFN BP(ND) in ventral striatum, putamen and caudate. When sex and smoking were added as covariates to the model, these correlations were strengthened and there was a significant correlation with the hypothalamus. There were no significant correlations between ACTH and any volumes of interest. The opioid receptor antagonist naloxone is not merely a non-specific pharmacologic activator of the HPA axis; it provides information about individual differences in opioid receptor availability.
authors.affiliation: Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, United States. gwand@jhmi.edu
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wand
authors.forename: Elise M
authors.initials: EM
authors.lastname: Weerts
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kuwabara
authors.forename: J James
authors.initials: JJ
authors.lastname: Frost
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Xu
authors.forename: Mary E
authors.initials: ME
authors.lastname: McCaul
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005544:Forecasting; D006262:Health; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009928:Organ Specificity / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects; D011859:Radiography; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D006854:Hydrocortisone