Devine D P, Watson S J, Akil H
Department of Psychology, University of Florida, Gainesville, 32611-2250, USA.
Neuroscience. 2001;102(3):541-53. doi: 10.1016/s0306-4522(00)00517-0.
We examined the effects of the neuropeptide nociceptin/orphanin FQ on activity of the limbic-hypothalamic-pituitary-adrenal axis (also known as the stress axis) in rats. This axis regulates important metabolic functions, and initiates critical neuroendocrine responses that cope with environmental threats and challenges to homeostatic functioning. Disregulation of the limbic-hypothalamic-pituitary-adrenal axis is associated with impaired physical and psychological health. In the present experiments, rats were treated with intracerebroventricular injections of nociceptin/orphanin FQ in the presence or absence of acute stressors. Plasma adrenocorticotrophic hormone and corticosterone concentrations were assayed 15 or 30min after injections. In the rats that were not exposed to stress, nociceptin/orphanin FQ produced dose-orderly elevations of circulating adrenocorticotrophic hormone and corticosterone concentrations. These effects were also found after administration of the nociceptin/orphanin FQ analogues, des-Phe orphanin FQ and [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin((1-13))NH(2). In rats that were exposed to the mild stress of a novel environment, nociceptin/orphanin FQ administration enhanced the stress-induced elevations of plasma adrenocorticotrophic hormone concentrations and prolonged the stress-induced elevations of plasma corticosterone concentrations. In rats that were exposed to restraint stress, nociceptin/orphanin FQ administration did not augment the stress-induced elevations in plasma hormones, perhaps because of a ceiling effect. We conclude that administration of nociceptin/orphanin FQ activates neuroendocrine activity of the limbic-hypothalamic-pituitary-adrenal axis even in the absence of a stressor, and may delay the shutdown of these physiological responses after exposure to acute mild stress. In light of the known functions of this axis, it appears that nociceptin/orphanin FQ participates in the regulation of important metabolic functions, and may be implicated in physiological responses to stress. This interaction between nociceptin/orphanin FQ and the limbic-hypothalamic-pituitary-adrenal axis implicates nociceptin/orphanin FQ in important aspects of physiological and psychological well-being.
我们研究了神经肽痛敏肽/孤啡肽FQ对大鼠边缘系统-下丘脑-垂体-肾上腺轴（也称为应激轴）活性的影响。该轴调节重要的代谢功能，并启动关键的神经内分泌反应以应对环境威胁和对体内平衡功能的挑战。边缘系统-下丘脑-垂体-肾上腺轴失调与身心健康受损有关。在本实验中，对大鼠进行脑室内注射痛敏肽/孤啡肽FQ，注射时存在或不存在急性应激源。注射后15或30分钟测定血浆促肾上腺皮质激素和皮质酮浓度。在未暴露于应激的大鼠中，痛敏肽/孤啡肽FQ使循环中的促肾上腺皮质激素和皮质酮浓度呈剂量依赖性升高。在给予痛敏肽/孤啡肽FQ类似物、去苯丙氨酸孤啡肽FQ和[苯丙氨酸(1)ψ(CH₂-NH)甘氨酸(2)]痛敏肽((1-13))NH₂后也发现了这些作用。在暴露于新环境轻度应激的大鼠中，给予痛敏肽/孤啡肽FQ可增强应激诱导的血浆促肾上腺皮质激素浓度升高，并延长应激诱导的血浆皮质酮浓度升高时间。在暴露于束缚应激的大鼠中，给予痛敏肽/孤啡肽FQ并未增强应激诱导的血浆激素升高，这可能是由于存在上限效应。我们得出结论，即使在没有应激源的情况下，给予痛敏肽/孤啡肽FQ也会激活边缘系统-下丘脑-垂体-肾上腺轴的神经内分泌活性，并且可能会延迟暴露于急性轻度应激后这些生理反应的终止。鉴于该轴的已知功能，痛敏肽/孤啡肽FQ似乎参与了重要代谢功能的调节，并且可能与应激的生理反应有关。痛敏肽/孤啡肽FQ与边缘系统-下丘脑-垂体-肾上腺轴之间的这种相互作用表明痛敏肽/孤啡肽FQ在生理和心理健康的重要方面发挥作用。
