Positron Emission Tomography Imaging of Mu- and Delta-Opioid Receptor Binding in Alcohol-Dependent and Healthy Control Subjects
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...
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| Published in | Alcoholism, clinical and experimental research Vol. 35; no. 12; pp. 2162 - 2173 |
|---|---|
| Main Authors | , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Publishing Ltd
01.12.2011
Wiley |
| Subjects | |
| Online Access | Get full text |
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| 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 (BPND) 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 BPND and craving in several brain regions in alcohol‐dependent subjects. Groups did not differ in [11C]MeNTL BPND; however, [11C]MeNTL BPND in caudate was positively correlated with recent alcohol drinking in alcohol‐dependent subjects.
Conclusions: Our observation of higher [11C]CFN BPND 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 BPND 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 BPND 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 BPND is consistent with a prominent role of the MOR in alcohol dependence. |
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| AbstractList | 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 (BPND) 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 BPND and craving in several brain regions in alcohol-dependent subjects. Groups did not differ in [11C]MeNTL BPND; however, [11C]MeNTL BPND in caudate was positively correlated with recent alcohol drinking in alcohol-dependent subjects. Conclusions: Our observation of higher [11C]CFN BPND 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 BPND 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 BPND 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 BPND is consistent with a prominent role of the MOR in alcohol dependence. 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. 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 [(11)C]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 [(11)C]methylnaltrindole (MeNTL). Volumes of interest and statistical parametric mapping analyses indicated that alcohol-dependent subjects had significantly higher [(11)C]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 [(11)C]CFN BP(ND) and craving in several brain regions in alcohol-dependent subjects. Groups did not differ in [(11)C]MeNTL BP(ND) ; however, [(11)C]MeNTL BP(ND) in caudate was positively correlated with recent alcohol drinking in alcohol-dependent subjects. Our observation of higher [(11)C]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 [(11)C]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 [(11)C]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 [(11)C]CFN BP(ND) is consistent with a prominent role of the MOR in alcohol dependence. 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.BACKGROUNDThe 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.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 [(11)C]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 [(11)C]methylnaltrindole (MeNTL).METHODSAlcohol-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 [(11)C]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 [(11)C]methylnaltrindole (MeNTL).Volumes of interest and statistical parametric mapping analyses indicated that alcohol-dependent subjects had significantly higher [(11)C]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 [(11)C]CFN BP(ND) and craving in several brain regions in alcohol-dependent subjects. Groups did not differ in [(11)C]MeNTL BP(ND) ; however, [(11)C]MeNTL BP(ND) in caudate was positively correlated with recent alcohol drinking in alcohol-dependent subjects.RESULTSVolumes of interest and statistical parametric mapping analyses indicated that alcohol-dependent subjects had significantly higher [(11)C]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 [(11)C]CFN BP(ND) and craving in several brain regions in alcohol-dependent subjects. Groups did not differ in [(11)C]MeNTL BP(ND) ; however, [(11)C]MeNTL BP(ND) in caudate was positively correlated with recent alcohol drinking in alcohol-dependent subjects.Our observation of higher [(11)C]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 [(11)C]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 [(11)C]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 [(11)C]CFN BP(ND) is consistent with a prominent role of the MOR in alcohol dependence.CONCLUSIONSOur observation of higher [(11)C]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 [(11)C]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 [(11)C]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 [(11)C]CFN BP(ND) is consistent with a prominent role of the MOR in alcohol dependence. 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 (BPND) 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 BPND and craving in several brain regions in alcohol‐dependent subjects. Groups did not differ in [11C]MeNTL BPND; however, [11C]MeNTL BPND in caudate was positively correlated with recent alcohol drinking in alcohol‐dependent subjects. Conclusions: Our observation of higher [11C]CFN BPND 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 BPND 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 BPND 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 BPND is consistent with a prominent role of the MOR in alcohol dependence. 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 [ 11 C]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 [ 11 C]methylnaltrindole (MeNTL). Results: Volumes of interest and statistical parametric mapping analyses indicated that alcohol‐dependent subjects had significantly higher [ 11 C]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 [ 11 C]CFN BP ND and craving in several brain regions in alcohol‐dependent subjects. Groups did not differ in [ 11 C]MeNTL BP ND ; however, [ 11 C]MeNTL BP ND in caudate was positively correlated with recent alcohol drinking in alcohol‐dependent subjects. Conclusions: Our observation of higher [ 11 C]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 [ 11 C]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 [ 11 C]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 [ 11 C]CFN BP ND is consistent with a prominent role of the MOR in alcohol dependence. |
| Author | McCaul, Mary E. Wand, Gary S. Dannals, Robert F. Hilton, John Weerts, Elise M. Kuwabara, Hiroto Munro, Cynthia A. Frost, J. James |
| Author_xml | – sequence: 1 givenname: Elise M. surname: Weerts fullname: Weerts, Elise M. organization: From the Department of Psychiatry and Behavioral Sciences (EMW, GSW, CAM, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine (GSW, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Radiology (HK, RFD, JH, JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland – sequence: 2 givenname: Gary S. surname: Wand fullname: Wand, Gary S. organization: From the Department of Psychiatry and Behavioral Sciences (EMW, GSW, CAM, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine (GSW, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Radiology (HK, RFD, JH, JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland – sequence: 3 givenname: Hiroto surname: Kuwabara fullname: Kuwabara, Hiroto organization: From the Department of Psychiatry and Behavioral Sciences (EMW, GSW, CAM, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine (GSW, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Radiology (HK, RFD, JH, JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland – sequence: 4 givenname: Cynthia A. surname: Munro fullname: Munro, Cynthia A. organization: From the Department of Psychiatry and Behavioral Sciences (EMW, GSW, CAM, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine (GSW, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Radiology (HK, RFD, JH, JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland – sequence: 5 givenname: Robert F. surname: Dannals fullname: Dannals, Robert F. organization: From the Department of Psychiatry and Behavioral Sciences (EMW, GSW, CAM, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine (GSW, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Radiology (HK, RFD, JH, JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland – sequence: 6 givenname: John surname: Hilton fullname: Hilton, John organization: From the Department of Psychiatry and Behavioral Sciences (EMW, GSW, CAM, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine (GSW, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Radiology (HK, RFD, JH, JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland – sequence: 7 givenname: J. James surname: Frost fullname: Frost, J. James organization: From the Department of Psychiatry and Behavioral Sciences (EMW, GSW, CAM, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine (GSW, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Radiology (HK, RFD, JH, JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland – sequence: 8 givenname: Mary E. surname: McCaul fullname: McCaul, Mary E. organization: From the Department of Psychiatry and Behavioral Sciences (EMW, GSW, CAM, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine (GSW, MEM), The Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Radiology (HK, RFD, JH, JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Neuroscience (JJF), The Johns Hopkins University School of Medicine, Baltimore, Maryland |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25254307$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/21689118$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | Copyright © 2011 by the Research Society on Alcoholism 2015 INIST-CNRS Copyright © 2011 by the Research Society on Alcoholism. |
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| Issue | 12 |
| Keywords | Human Binding Poison withdrawal Alcoholism Central nervous system Brain Imaging δ Opioid receptor Abstinence Encephalon Alcoholic beverage Carfentanil Dependence Disintoxication Medical imagery Naltrindole Positron emission tomography Emission tomography |
| Language | English |
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| Snippet | Background: The endogenous opioid system plays a significant role in alcohol dependence. The goal of the current study was to investigate regional brain... Background: The endogenous opioid system plays a significant role in alcohol dependence. The goal of the current study was to investigate regional brain... 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... |
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| SubjectTerms | Abstinence Addictive behaviors Adult Adult and adolescent clinical studies Alcoholism Alcoholism - diagnostic imaging Alcoholism - metabolism Alcoholism and acute alcohol poisoning Biological and medical sciences Brain - diagnostic imaging Brain - metabolism Brain Imaging Carfentanil Case-Control Studies Female Humans Male Medical sciences Middle Aged Naltrindole Positron-Emission Tomography - methods Protein Binding Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Receptors, Opioid, delta - metabolism Receptors, Opioid, mu - metabolism Toxicology Young Adult |
| Title | Positron Emission Tomography Imaging of Mu- and Delta-Opioid Receptor Binding in Alcohol-Dependent and Healthy Control Subjects |
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