Positron Emission Tomography Imaging of Mu- and Delta-Opioid Receptor Binding in Alcohol-Dependent and Healthy Control Subjects

Research output: Contribution to journalArticle

Abstract

Background: The endogenous opioid system plays a significant role in alcohol dependence. The goal of the current study was to investigate regional brain mu-opioid receptor (MOR) and delta-opioid receptor (DOR) availability in recently abstinent alcohol-dependent and age-matched healthy control men and women with positron emission tomography (PET) imaging. Methods: Alcohol-dependent subjects completed an inpatient protocol, which included medically supervised withdrawal and PET imaging on day 5 of abstinence. Control subjects completed PET imaging following an overnight stay. PET scans with the MOR-selective ligand [ 11C]carfentanil (CFN) were completed in 25 alcohol-dependent and 30 control subjects. Most of these same subjects (20 alcohol-dependent subjects and 18 controls) also completed PET scans with the DOR-selective ligand [ 11C]methylnaltrindole (MeNTL). Results: Volumes of interest and statistical parametric mapping analyses indicated that alcohol-dependent subjects had significantly higher [ 11C]CFN binding potential (BP ND) than healthy controls in multiple brain regions including the ventral striatum when adjusting for age, gender, and smoking status. There was an inverse relationship between [ 11C]CFN BP ND and craving in several brain regions in alcohol-dependent subjects. Groups did not differ in [ 11C]MeNTL BP ND; however, [ 11C]MeNTL BP ND in caudate was positively correlated with recent alcohol drinking in alcohol-dependent subjects. Conclusions: Our observation of higher [ 11C]CFN BP ND in alcohol-dependent subjects can result from up-regulation of MOR and/or reduction in endogenous opioid peptides following long-term alcohol consumption, dependence, and/or withdrawal. Alternatively, the higher [ 11C]CFN BP ND in alcohol-dependent subjects may be an etiological difference that predisposed these individuals to alcohol dependence or may have developed as a result of increased exposure to childhood adversity, stress, and other environmental factors known to increase MOR. Although the direction of group differences in [ 11C]MeNTL BP ND was similar in many brain regions, differences did not achieve statistical significance, perhaps as a result of our limited sample size. Additional research is needed to further clarify these relationships. The finding that alcohol-dependent subjects had higher [ 11C]CFN BP ND is consistent with a prominent role of the MOR in alcohol dependence.

Original languageEnglish (US)
Pages (from-to)2162-2173
Number of pages12
JournalAlcoholism: Clinical and Experimental Research
Volume35
Issue number12
DOIs
StatePublished - Dec 2011

Fingerprint

carfentanil
delta Opioid Receptor
Positron emission tomography
mu Opioid Receptor
Positron-Emission Tomography
Healthy Volunteers
Alcohols
Imaging techniques
Alcoholism
Brain
Alcohol Drinking
Ligands
Opioid Peptides
Individuality
Sample Size
Opioid Analgesics
Inpatients
Up-Regulation
Smoking
Observation

Keywords

  • Abstinence
  • Alcoholism
  • Brain Imaging
  • Carfentanil
  • Naltrindole

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Toxicology

Cite this

@article{a906564cc62e455a810c3d4060991a51,
title = "Positron Emission Tomography Imaging of Mu- and Delta-Opioid Receptor Binding in Alcohol-Dependent and Healthy Control Subjects",
abstract = "Background: The endogenous opioid system plays a significant role in alcohol dependence. The goal of the current study was to investigate regional brain mu-opioid receptor (MOR) and delta-opioid receptor (DOR) availability in recently abstinent alcohol-dependent and age-matched healthy control men and women with positron emission tomography (PET) imaging. Methods: Alcohol-dependent subjects completed an inpatient protocol, which included medically supervised withdrawal and PET imaging on day 5 of abstinence. Control subjects completed PET imaging following an overnight stay. PET scans with the MOR-selective ligand [ 11C]carfentanil (CFN) were completed in 25 alcohol-dependent and 30 control subjects. Most of these same subjects (20 alcohol-dependent subjects and 18 controls) also completed PET scans with the DOR-selective ligand [ 11C]methylnaltrindole (MeNTL). Results: Volumes of interest and statistical parametric mapping analyses indicated that alcohol-dependent subjects had significantly higher [ 11C]CFN binding potential (BP ND) than healthy controls in multiple brain regions including the ventral striatum when adjusting for age, gender, and smoking status. There was an inverse relationship between [ 11C]CFN BP ND and craving in several brain regions in alcohol-dependent subjects. Groups did not differ in [ 11C]MeNTL BP ND; however, [ 11C]MeNTL BP ND in caudate was positively correlated with recent alcohol drinking in alcohol-dependent subjects. Conclusions: Our observation of higher [ 11C]CFN BP ND in alcohol-dependent subjects can result from up-regulation of MOR and/or reduction in endogenous opioid peptides following long-term alcohol consumption, dependence, and/or withdrawal. Alternatively, the higher [ 11C]CFN BP ND in alcohol-dependent subjects may be an etiological difference that predisposed these individuals to alcohol dependence or may have developed as a result of increased exposure to childhood adversity, stress, and other environmental factors known to increase MOR. Although the direction of group differences in [ 11C]MeNTL BP ND was similar in many brain regions, differences did not achieve statistical significance, perhaps as a result of our limited sample size. Additional research is needed to further clarify these relationships. The finding that alcohol-dependent subjects had higher [ 11C]CFN BP ND is consistent with a prominent role of the MOR in alcohol dependence.",
keywords = "Abstinence, Alcoholism, Brain Imaging, Carfentanil, Naltrindole",
author = "Elise Weerts and Wand, {Gary S} and Hiroto Kuwabara and Cynthia Munro and Dannals, {Robert F} and John Hilton and Frost, {J. James} and McCaul, {Mary Elizabeth}",
year = "2011",
month = "12",
doi = "10.1111/j.1530-0277.2011.01565.x",
language = "English (US)",
volume = "35",
pages = "2162--2173",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "12",

}

TY - JOUR

T1 - Positron Emission Tomography Imaging of Mu- and Delta-Opioid Receptor Binding in Alcohol-Dependent and Healthy Control Subjects

AU - Weerts, Elise

AU - Wand, Gary S

AU - Kuwabara, Hiroto

AU - Munro, Cynthia

AU - Dannals, Robert F

AU - Hilton, John

AU - Frost, J. James

AU - McCaul, Mary Elizabeth

PY - 2011/12

Y1 - 2011/12

N2 - Background: The endogenous opioid system plays a significant role in alcohol dependence. The goal of the current study was to investigate regional brain mu-opioid receptor (MOR) and delta-opioid receptor (DOR) availability in recently abstinent alcohol-dependent and age-matched healthy control men and women with positron emission tomography (PET) imaging. Methods: Alcohol-dependent subjects completed an inpatient protocol, which included medically supervised withdrawal and PET imaging on day 5 of abstinence. Control subjects completed PET imaging following an overnight stay. PET scans with the MOR-selective ligand [ 11C]carfentanil (CFN) were completed in 25 alcohol-dependent and 30 control subjects. Most of these same subjects (20 alcohol-dependent subjects and 18 controls) also completed PET scans with the DOR-selective ligand [ 11C]methylnaltrindole (MeNTL). Results: Volumes of interest and statistical parametric mapping analyses indicated that alcohol-dependent subjects had significantly higher [ 11C]CFN binding potential (BP ND) than healthy controls in multiple brain regions including the ventral striatum when adjusting for age, gender, and smoking status. There was an inverse relationship between [ 11C]CFN BP ND and craving in several brain regions in alcohol-dependent subjects. Groups did not differ in [ 11C]MeNTL BP ND; however, [ 11C]MeNTL BP ND in caudate was positively correlated with recent alcohol drinking in alcohol-dependent subjects. Conclusions: Our observation of higher [ 11C]CFN BP ND in alcohol-dependent subjects can result from up-regulation of MOR and/or reduction in endogenous opioid peptides following long-term alcohol consumption, dependence, and/or withdrawal. Alternatively, the higher [ 11C]CFN BP ND in alcohol-dependent subjects may be an etiological difference that predisposed these individuals to alcohol dependence or may have developed as a result of increased exposure to childhood adversity, stress, and other environmental factors known to increase MOR. Although the direction of group differences in [ 11C]MeNTL BP ND was similar in many brain regions, differences did not achieve statistical significance, perhaps as a result of our limited sample size. Additional research is needed to further clarify these relationships. The finding that alcohol-dependent subjects had higher [ 11C]CFN BP ND is consistent with a prominent role of the MOR in alcohol dependence.

AB - Background: The endogenous opioid system plays a significant role in alcohol dependence. The goal of the current study was to investigate regional brain mu-opioid receptor (MOR) and delta-opioid receptor (DOR) availability in recently abstinent alcohol-dependent and age-matched healthy control men and women with positron emission tomography (PET) imaging. Methods: Alcohol-dependent subjects completed an inpatient protocol, which included medically supervised withdrawal and PET imaging on day 5 of abstinence. Control subjects completed PET imaging following an overnight stay. PET scans with the MOR-selective ligand [ 11C]carfentanil (CFN) were completed in 25 alcohol-dependent and 30 control subjects. Most of these same subjects (20 alcohol-dependent subjects and 18 controls) also completed PET scans with the DOR-selective ligand [ 11C]methylnaltrindole (MeNTL). Results: Volumes of interest and statistical parametric mapping analyses indicated that alcohol-dependent subjects had significantly higher [ 11C]CFN binding potential (BP ND) than healthy controls in multiple brain regions including the ventral striatum when adjusting for age, gender, and smoking status. There was an inverse relationship between [ 11C]CFN BP ND and craving in several brain regions in alcohol-dependent subjects. Groups did not differ in [ 11C]MeNTL BP ND; however, [ 11C]MeNTL BP ND in caudate was positively correlated with recent alcohol drinking in alcohol-dependent subjects. Conclusions: Our observation of higher [ 11C]CFN BP ND in alcohol-dependent subjects can result from up-regulation of MOR and/or reduction in endogenous opioid peptides following long-term alcohol consumption, dependence, and/or withdrawal. Alternatively, the higher [ 11C]CFN BP ND in alcohol-dependent subjects may be an etiological difference that predisposed these individuals to alcohol dependence or may have developed as a result of increased exposure to childhood adversity, stress, and other environmental factors known to increase MOR. Although the direction of group differences in [ 11C]MeNTL BP ND was similar in many brain regions, differences did not achieve statistical significance, perhaps as a result of our limited sample size. Additional research is needed to further clarify these relationships. The finding that alcohol-dependent subjects had higher [ 11C]CFN BP ND is consistent with a prominent role of the MOR in alcohol dependence.

KW - Abstinence

KW - Alcoholism

KW - Brain Imaging

KW - Carfentanil

KW - Naltrindole

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U2 - 10.1111/j.1530-0277.2011.01565.x

DO - 10.1111/j.1530-0277.2011.01565.x

M3 - Article

C2 - 21689118

AN - SCOPUS:81855193937

VL - 35

SP - 2162

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JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 12

ER -