The Role of Nociceptin in Opioid Regulation of Brain Functions

— The review summarizes current knowledge on the role of the nociceptin/orphanin (N/OFQ) system in the regulation of brain functions. The nociceptin receptor (NOPr) was originally identified in 1994 (Bunzow et al., 1994; Mollereau et al., 1994). In 1995, an endogenous peptide consisting of 17 residues was found as a high affinity ligand for the NOPr (Reinscheid et al., 1995). N/OFQ has a broad spectrum of activity and can act as an opioid-like as well as an anti-opioid peptide. The high level of N/OFQ and NOPr mRNA expression in the limbic brain regions, suggests that the N/OFQ system is involved in regulation of emotions, reward, pain sensitivity, stress responsiveness, sexual behavior and aggression. It is suggested that N/OFQ may be also involved in regulation of addiction; however, it is still not well understood whether an increased vulnerability to drugs of abuse may be associated with dysregulation of this system. Further research is clearly needed for the development of new drugs aimed at pharmacotherapy of depression, anxiety disorders, alcohol and other types of addiction.