Fernandez Fabian, Misilmeri Michael A, Felger Jennifer C, Devine Darragh P
Department of Psychology, University of Florida, Gainesville, FL 32611-2250, USA.
Neuropsychopharmacology. 2004 Jan;29(1):59-71. doi: 10.1038/sj.npp.1300308.
Intracranial administration of nociceptin/orphanin FQ (N/OFQ) increases circulating concentrations of adrenocorticotrophic hormone and corticosterone in unstressed rats, and elevates the responsiveness of these hormones during mild stress. Furthermore, N/OFQ and its cognate receptor are both abundant in a variety of limbic nuclei, and stress exposure decreases neuronal N/OFQ content in forebrain neurons. In light of these and other findings, we examined the potential involvement of N/OFQ in regulation of anxiety-related behaviors in rats. In the open field, elevated plus maze, and dark-light neophobic tests, intracerebroventricular N/OFQ (1.0 pmole-1.0 nmole) increased the expression of anxiety-related behaviors. Specifically, N/OFQ increased the latency to enter, decreased the number of entries into, and decreased the time spent in the exposed or brightly lit environments of all three tests. N/OFQ also enhanced thigmotactic responses in the open field test. The effects of diazepam and of the benzodiazepine inverse agonist FG 7142 were also assessed in independent groups of rats. In all three tests, the behavioral effects of N/OFQ resembled the anxiogenic actions of FG 7142, and contrasted with the anxiolytic actions of diazepam. N/OFQ administration also increased circulating concentrations of corticosterone during anxiety testing, in comparison with the concentrations in vehicle-treated controls. We conclude that N/OFQ administration is anxiogenic, and elevates responsiveness of the hypothalamic pituitary-adrenal axis during neophobic tests of anxiety. This supports the possibility that N/OFQ neurotransmission participates in processing of emotionally-salient and stressful stimuli, and suggests that normal functioning of the N/OFQ system may be important in physiological and psychological well-being.
向未受应激的大鼠颅内注射孤啡肽/孤啡肽FQ（N/OFQ）可提高促肾上腺皮质激素和皮质酮的循环浓度，并增强这些激素在轻度应激期间的反应性。此外，N/OFQ及其同源受体在多种边缘核中均大量存在，应激暴露会降低前脑神经元中的神经元N/OFQ含量。鉴于这些及其他发现，我们研究了N/OFQ在调节大鼠焦虑相关行为中的潜在作用。在旷场试验、高架十字迷宫试验和明暗新物恐惧试验中，脑室内注射N/OFQ（1.0皮摩尔 - 1.0纳摩尔）会增加焦虑相关行为的表现。具体而言，N/OFQ增加了进入的潜伏期，减少了进入次数，并减少了在所有三项试验中暴露或明亮环境中停留的时间。N/OFQ还增强了旷场试验中的趋触性反应。还在独立的大鼠组中评估了地西泮和苯二氮䓬反向激动剂FG 7142的作用。在所有三项试验中，N/OFQ的行为效应类似于FG 7142的致焦虑作用，与地西泮的抗焦虑作用形成对比。与注射赋形剂的对照组相比，焦虑测试期间注射N/OFQ还会增加皮质酮的循环浓度。我们得出结论，注射N/OFQ具有致焦虑作用，并在新物恐惧焦虑试验中提高下丘脑 - 垂体 - 肾上腺轴的反应性。这支持了N/OFQ神经传递参与处理情绪显著和应激刺激的可能性，并表明N/OFQ系统的正常功能可能对生理和心理健康很重要。
