In vivo imaging of corticotropin releasing factor-nociceptin receptor interactions

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

Basic investigations postulate that an imbalance between neurotransmitters regulating the stress and anti-stress systems underlie negative reinforcement and relapse in addiction. Nociceptin, which binds to the nociceptin/orphanin FQ peptide (NOP) receptor, is one such neuropeptide transmitter that exerts its anti-stress effects by counteracting the functional effects of corticotropin releasing factor (CRF), the primary stress-mediating neuropeptide transmitter in the brain. Basic investigations suggest that CRF and nociceptin facilitate and inhibit anxiety-like behaviors respectively. Convergent with this is data from animal models of alcoholism that support increased CRF and decreased nociceptin levels in the extended amygdala as the reason for anxiety-like behaviors that underlie relapse in addiction. This postulation is further supported by the ability of CRF1 receptor antagonists and NOP receptor agonists to blunt the reinforcing and motivational effects of alcohol on a range of addictive behaviors. Thus, it is of considerable interest to develop a methodology to examine CRF- NOP interactions in human addicts. Here, we will evaluate in healthy humans with [11C]NOP-1A and PET whether hydrocortisone-induced increases in amygdala CRF leads to altered NOP receptor binding. This experiment will for the first time document an in vivo interaction between CRF and NOP, and set the stage for evaluating whether this interaction is abnormal in addiction in future investigations. !