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 and women with positron emission tomography (PET) imaging. Methods: Alcohol-dependent subjectsCompleted an inpatient protocol, which included medically supervised withdrawal and PET imaging on day 5 of abstinence.Control subjectsCompleted PET imaging following an overnight stay. PET scans with the MOR-selective ligand [C-11]Carfentanil (CFN) wereCompleted in 25 alcohol-dependent and 30Control subjects. Most of these same subjects (20 alcohol-dependent subjects and 18Controls) alsoCompleted PET scans with the DOR-selective ligand [C-11] methylnaltrindole (MeNTL). Results: Volumes of interest and statistical parametric mapping analyses indicated that alcohol- dependent subjects had significantly higher [C-11]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 [C-11]CFN BPND andCraving in several brain regions in alcohol-dependent subjects. Groups did not differ in [C-11] MeNTL BPND; however, [C-11] MeNTL BPND inCaudate was positivelyCorrelated with recent alcohol drinking in alcohol-dependent subjects. Conclusions: Our observation of higher [C-11]CFN BPND in alcohol-dependent subjectsCan result from up-regulation of MOR and / or reduction in endogenous opioid peptides following long-term alcoholConsumption, dependence, and / or withdrawal. Alternatively, the higher [C-11]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 toChildhood adversity, stress, and other environmental factors known to increase MOR. Although the direction of group differences in [C-11] 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 furtherClarify these relationships. The finding that alcohol-dependent subjects had higher [C-11]CFN BPND isConsistent with a prominent role of the MOR in alcohol dependence.