The Role of Orphanin FQ/Nociceptin in Neuroplasticity: Relationship to Stress, Anxiety and Neuroinflammation

• Main Authors: Elyse M Mallimo, Alexander W Kusnecov
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2013-10-01
• Series: Frontiers in Cellular Neuroscience
• Subjects: Anxiety; Astrocytes; Cytokines; Fear; Glucocorticoids; Immune System
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fncel.2013.00173/full

The neuropeptide, orphanin FQ/nociceptin (OFQ/N or simply, nociceptin), is expressed in both neuronal and nonneuronaltissue, including the immune system. In the brain, OFQ/N has been investigated in relation to stress, anxiety,learning and memory, and addiction. More recently, it has also been found that OFQ/N influences glial cell functions,including oligodendrocytes, astrocytes and microglial cells. However, this latter research is relatively small, butpotentially important, when observations regarding the relationship of OFQ/N to stress and emotional functions is takeninto consideration and integrated with the growing evidence for its involvement in cells that mediate inflammatory events.This review will first provide an overview and understanding of how OFQ/N has been implicated in the HPA axisresponse to stress, followed by an understanding of its influence on natural and learned anxiety-like behavior. Whatemerges from an examination of the literature is a neuropeptide that appears to counteract anxiogenic influences, butparadoxically, without attenuating HPA axis responses generated in response to stress. Studies utilized both centraladministration of OFQ/N, which was shown to activate the HPA axis, as well as antagonism of NOP-R, the OFQ/Nreceptor. In contrast, antagonist or transgenic OFQ/N or NOP-R knockout studies, showed augmentation of HPA axisresponses to stress, suggesting that OFQ/N may be needed to control the magnitude of the HPA axis response to stress.Investigations of behavior in standard exploratory tests of anxiogenic behavior (eg., elevated plus maze) or learned fearresponses have suggested that OFQ/N is needed to attenuate fear or anxiety-like behavior. However, some discrepantobservations, in particular, those that involve appetitive behaviors, suggest a failure of NOP-R deletion to increaseanxiety.