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 nociceptive opioid peptide (NOP) receptor, is one such neuropeptide transmitter that exerts anti-stress effects by counteracting the functional effects of endogenous corticotropin releasing factor in the brain. Post-mortem studies in rodents and human alcoholics show decreased nociceptin levels in the hippocampus and amygdala. Furthermore, activation of NOP receptors by nociceptin and synthetic NOP agonists (such as buprenorphine, MT-7716, etc.,) blunt the reinforcing and motivational effects of alcohol on a range of addictive behaviors such as self-administration, conditioned place preference, and cue- and stress- induced alcohol reinstatement. Here, we will use [11C]NOP-1A and positron emission tomography to contrast the in vivo status of NOP receptors in human alcoholics with that measured in matched controls. In addition, alcoholics will be followed for twelve weeks with urine alcohol metabolite tests to determine relapse to alcohol while they undergo a standardized contingency management treatment protocol. This will allow us to establish the relationship between NOP receptor availability and stress, anxiety and relapse to alcohol.
The aims proposed in this application capitalize on the recent validation of [11C]NOP-1A as a selective NOP receptor PET radiotracer and will inform us of the in vivo status and clinical relevance of NOP receptors in alcoholism. It also has the potential to inform medication development efforts to prevent relapse in alcoholism.
| Narendran, Rajesh; Ciccocioppo, Roberto; Lopresti, Brian et al. (2018) Nociceptin Receptors in Alcohol Use Disorders: A Positron Emission Tomography Study Using [11C]NOP-1A. Biol Psychiatry 84:708-714 |
