Nociceptin and Stress: A Review of 30 Years of Experimental Research

The endogenous opioid system, known for its unique role in the complex neurochemical regulation of physiological functions and behavior, is a bright illustration of the concept of the peptide continuum proposed by I.P. Ashmarin [1,2]. The last of the discovered opioid neuropeptides was nociceptin/orphanin (N/OFQ), an endogenous ligand of the nociceptin opioid-like receptor (NOP), whose functions are multiple and still not completely clear. In contrast to the active expression of the receptor in various brain regions, N/OFQ expression is more limited and predominantly localized in structures associated with stress and regulation of dopamine neurotransmission. This review presents a current view on the role of N/OFQ and NOP in the modulation of stress and related mental illnesses, including post-traumatic stress disorder. Preclinical data suggest that the use of both NOP agonists and antagonists may represent a promising approach to the treatment of these diseases.