Nociceptin/orphanin FQ regulates neuroendocrine function of the limbic-hypothalamic-pituitary-adrenal axis

We examined the effects of the neuropeptide nociceptin/orphanin FQ on activ ity of the limbic-hypothalamic-pituitary-adrenal axis (also known as the st ress axis) in rats. This axis regulates important metabolic functions, and initiates critical neuroendocrine responses that cope with environmental th reats and challenges to homeostatic functioning. Disregulation of the limbi c-hypothalamic-pituitary-adrenal axis is associated with impaired physical and psychological health. In the present experiments. rats were treated wit h intracerebroventricular injections of nociceptin/orphanin FQ in the prese nce or absence of acute stressors. Plasma adrenocorticotrophic hormone and corticosterone concentrations were assayed 15 or 30 min after injections. I n the rats that were not exposed to stress, nociceptin/orphanin FQ produced dose-orderly elevations of circulating adrenocorticotrophic hormone and co rticosterone concentrations. These effects were also found after administra tion of the nociceptin/orphanin FQ analogues, des-Phe orphanin FQ and [Phe( 1)psi (CH2-NH)Gly(2)] nociceptin((1-13))NH(2). In rats that were exposed to the mild stress of a novel environment, nociceptin/orphanin FQ administrat ion enhanced the stress-induced elevations of plasma adrenocorticotrophic h ormone concentrations and prolonged the stress-induced elevations of plasma corticosterone concentrations. In rats that were exposed to restraint stre ss, nociceptin/ orphanin FQ administration did not augment the stress-induc ed elevations in plasma hormones, perhaps because of a ceiling effect. We conclude that administration of nociceptin/orphanin FQ activates neuroen docrine activity of the limbic-hypothalamic-pituitary-adrenal axis even in the absence of a stressor, and map delay the shutdown of these physiologica l responses after exposure to acute mild stress. In light of the known func tions of this axis, it appears that nociceptin/orphanin FQ participates in the regulation of important metabolic functions, and may be implicated in p hysiological responses to stress. This interaction between nociceptin/orpha nin FQ and the limbic-hypothalamic-pituitary-adrenal axis implicates nocice ptin/orphanin FQ in important aspects of physiological and psychological we ll-being. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights rese rved.