Nociceptin receptors in alcohol use disorders: a PET study using [11 C]NOP-1A

Abstract Background The neuropeptide transmitter nociceptin, which binds to the nociceptin/orphanin FQ peptide (NOP) receptor, is a core component of the brain's anti-stress system. Nociceptin exerts its anti-stress 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 [11 C]NOP-1A and PET to measure the in vivo binding to NOP receptors in 15 DSM-IV alcohol-dependent humans and 15 healthy controls matched for age, gender, and smoking status. Alcohol-dependent individuals with no comorbid psychiatric, medical, or drug abuse disorders were scanned following two weeks of outpatient monitored abstinence (confirmed with 3x/week urine alcohol metabolite testing). [11 C]NOP-1A distribution volume (VT ) in regions of interest (including the amygdala, hippocampus, midbrain, striatal, and prefrontal cortical subdivisions) were measured with kinetic analysis using the arterial input function. Results Regional [11 C]NOP-1A VT in alcohol-dependence was not significantly different compared to healthy controls. No relationship between [11 C]NOP-1A VT and other clinical measures (including duration and severity of alcohol abuse, craving, 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.