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Biol Psychiatry. 2018 Nov 15;84(10):708-714. doi: 10.1016/j.biopsych.2017.05.019. Epub 2017 May 31.

Nociceptin Receptors in Alcohol Use Disorders: A Positron Emission Tomography Study Using [11C]NOP-1A.

Author information

1
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: narendranr@upmc.edu.
2
School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
3
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
4
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.

Abstract

BACKGROUND:

The neuropeptide transmitter nociceptin, which binds to the nociceptin/orphanin FQ peptide (NOP) receptor, is a core component of the brain's antistress system. Nociceptin exerts its antistress effect by counteracting the functions of corticotropin-releasing factor, the primary stress-mediating neuropeptide in the brain. Basic investigations support a role for medications that target nociceptin receptors in the treatment of alcohol use disorders. Thus, it is of high interest to measure the in vivo status of NOP receptors in individuals with alcohol use disorders.

METHODS:

Here, we used [11C]NOP-1A and positron emission tomography to measure the in vivo binding to NOP receptors in 15 alcohol-dependent humans as identified by DSM-IV and 15 healthy control subjects matched for age, sex, and smoking status. Alcohol-dependent individuals with no comorbid psychiatric, medical, or drug abuse disorders were scanned following 2 weeks of outpatient monitored abstinence (confirmed with three times per week urine alcohol metabolite testing). [11C]NOP-1A distribution volume in regions of interest (including the amygdala, hippocampus, and midbrain, striatal, and prefrontal cortical subdivisions) was measured with kinetic analysis using the arterial input function.

RESULTS:

Regional [11C]NOP-1A distribution volume in alcohol dependence was not significantly different compared with healthy control subjects. No relationship between [11C]NOP-1A distribution volume and other clinical measures (including duration and severity of alcohol abuse, craving, and anxiety or depressive symptoms) were significant after correction for the multiple hypotheses tested.

CONCLUSIONS:

The results of this study do not support alterations in the binding to NOP receptors in alcohol dependence. However, this finding does not necessarily rule out alterations in nociceptin transmission in alcohol dependence.

KEYWORDS:

Alcohol dependence; Antistress; Brain; Nociceptin/orphanin FQ peptide receptors; Positron emission tomography; [(11)C]NOP-1A

PMID:
28711193
PMCID:
PMC5711613
[Available on 2019-11-15]
DOI:
10.1016/j.biopsych.2017.05.019

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