@article{297327d802f14b1788c25458076eb61e,
title = "The relationship between naloxone-induced cortisol and mu opioid receptor availability in mesolimbic structures is disrupted in alcohol dependent subjects",
abstract = "The mu opioid receptor system is altered in alcohol dependent (AD) subjects. Cortisol responses to opioid receptor antagonists are assumed to impart information about opioid receptor activity. In the present study we examined naloxone-induced cortisol responses in 18 healthy control (HC) and 25 recently detoxified AD subjects and then correlated the cortisol response with mu opioid receptor availability across 15 brain regions using positron emission tomography (PET) and the mu opioid receptor selective ligand [11C] Carfentanil (CFN). On average the AD subjects required twice the dose of naloxone to induce a peak cortisol response compared to the HC subjects. Using the rising slope of the cortisol curve (placebo to peak) as a metric we then went on to examine the relationship between cortisol responses to naloxone and [11C]CFN BPND. There were significant negative relationships between cortisol and [11C]CFN binding potential (BPND) in multiple brain regions of HC subjects. However, cortisol responses did not correlate with [11C]CFN BPND across any brain region in AD subjects. In summary, naloxone imparts information about individual differences in mu opioid receptor availability throughout the mesolimbic system in healthy individuals. However pathways governing the relationship between naloxone-induced cortisol and mu opioid receptor availability are disrupted during early abstinence in AD subjects.",
keywords = "Alcoholism, Cortisol, HPA axis, Mu Opioid receptors, Naloxone, PET imaging",
author = "Wand, {Gary S.} and Weerts, {Elise M.} and Hiroto Kuwabara and Wong, {Dean F.} and Xiaoqiang Xu and McCaul, {Mary E.}",
note = "Funding Information: The National Institute of Alcohol Abuse and Alcoholism (NIAAA) provided financial support for research related to the subject matter of this manuscript from the grants R37AA12303 (PI: G.S. Wand) and R01AA11855 (PI:M.E. McCaul). Dr. Wand is the recipient of a gift fund from the Kenneth Lattman Foundation . Funding Information: Dr. Wand is the recipient of a gift fund from the Kenneth Lattman Foundation. He is an investigator in a post marketing study for Eli Lilly & Company, entitled The Global Hypopituitary Control and Complications Study (HypoCCS). He is an investigator in a post marketing study for Ipsen entitled, Somatuline Depot (lanreotide) Injection for Acromegaly (SODA). Dr. Wong is a consultant for Amgen. Between 2009 and present, Dr. Wong has received funding from the following companies: Acadia, Amgen, Avid, Biotie, Bristol Myers Squibb, GE, Intracellular, J&J, Lilly, Luhdeck, Merk, Orexigen, Otuska, Roche, Sanofi-Aventis and Sepracor. Dr. McCaul was principal investigator on a contract (A Phase 2 Study of LY2196044 Compared with Naltrexone and Placebo in the Treatment of Alcohol Dependence) funded by Lilly Research Laboratories; Drs. Weerts and Wand were co-investigators on this project. Dr. Kuwabara and Mr. Xu have no financial disclosures. ",
year = "2012",
month = sep,
doi = "10.1016/j.alcohol.2012.04.006",
language = "English",
volume = "46",
pages = "511--517",
journal = "Alcohol",
issn = "0741-8329",
number = "6",
}