• Alcohol. Clin. Exp. Res. · Dec 2011

    Positron emission tomography imaging of mu- and delta-opioid receptor binding in alcohol-dependent and healthy control subjects.

    • Elise M Weerts, Gary S Wand, Hiroto Kuwabara, Cynthia A Munro, Robert F Dannals, John Hilton, J James Frost, and Mary E McCaul.
    • Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. eweerts@jhmi.edu
    • Alcohol. Clin. Exp. Res. 2011 Dec 1;35(12):2162-73.

    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.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).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.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.Copyright © 2011 by the Research Society on Alcoholism.

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