ORPHANIN FQ ACTS AS AN ANXIOLYTIC TO ATTENUATE BEHAVIORAL-RESPONSES TO STRESS

Orphanin FQ (OFQ, Nociceptin) is a recently discovered 17-amino acid n europeptide that is structurally related to the opioid peptides but do es not bind opioid receptors. OFQ has been proposed to act as an anti- opioid peptide, but its widespread sites of action in the brain sugges t that it may have more general functions. Here we show that OFQ plays an important role in higher brain functions because it can act as an anxiolytic to attenuate the behavioral inhibition of animals acutely e xposed to stressful/anxiogenic environmental conditions. OFQ anxiolyti c-like effects were consistent across several behavioral paradigms gen erating different types of anxiety states in animals (light-dark prefe rence, elevated plus-maze, exploratory behavior of an unfamiliar envir onment, pharmacological anxiogenesis, operant conflict) and were obser ved at low nonsedating doses (0.1-3 nmol, intracerebroventricular). Li ke conventional anxiolytics, OFQ interfered with regular sensorimotor function at high doses (>3 nmol). Our results show that an important r ole of OFQ is to act as an endogenous regulator of acute anxiety respo nses. OFQ, probably in concert with other major neuropeptides, exerts a modulatory role on the central integration of stressful stimuli and, thereby, may modulate anxiety states generated by acute stress.