Imaging Nociceptin Opioid Peptide Receptors in Alcohol Use Disorder With [11C]NOP-1A and Positron Emission Tomography: Findings From a Second Cohort

Abstract

Background: Nociceptin, which binds to the nociceptin opioid peptide receptor (NOP), regulates stress and reward in addiction. In a previous [¹¹C]NOP-1A positron emission tomography (PET) study, we found no differences in NOP in non-treatment-seeking individuals with alcohol use disorder (AUD) relative to healthy control subjects Here, we evaluated NOP in treatment-seeking individuals with AUD to document its relationship with relapse to alcohol.

Methods: [¹¹C]NOP-1A distribution volume (V_T) was measured in recently abstinent individuals with AUD and healthy control subjects (n = 27/group) using an arterial input function-based kinetic analysis in brain regions that regulate reward and stress behaviors. Recent heavy drinking before PET was quantified using hair ethyl glucuronide (≥30 pg/mg was defined as heavy drinking). To document relapse, 22 subjects with AUD were followed with urine ethyl glucoronide tests (3/week) for 12 weeks after PET, where they were incentivized with money to abstain.

Results: There were no differences in [¹¹C]NOP-1A V_T between individuals with AUD and healthy control subjects. Individuals with AUD who drank heavily before the study had significantly lower V_T than those with no recent heavy drinking history. Significant negative correlations between V_T and the number of drinking days and the number of drinks consumed per drinking day in the 30 days before enrollment were also present. Individuals with AUD who relapsed (and dropped out) had significantly lower V_T than those who abstained for 12 weeks.

Conclusions: Lower NOP V_T in heavy drinking AUD predicted relapse to alcohol during a 12-week follow-up period. The results of this PET study support the need to investigate medications that act at NOP to prevent relapse in individuals with AUD.

Keywords: Alcohol use disorder (AUD) [(11)C]NOP-1A; Heavy drinking; Nociceptin (N/OFQ); Nociceptin opioid peptide receptors (NOP); Positron emission tomography; Relapse.