The purpose of this study was to examine the effects of stress and the role of locally infused anxiogenic-like neuropeptides galanin, CCK-8, vasopressin, substance P and neurokinin A, and anxiolytic-like peptides NPY, nociceptin/orphanin FQ, somatostatin and neurotensin, on modulation of noradrenaline (NA) and cAMP efflux monitored simultaneously by microdialysis in the medial prefronatal cortex of awake rats. Concentrations of cAMP were determined by a newly developed method based on derivatization of cAMP with 2-chloroacetaldehyde followed by HPLC with fluorescence detection. Local infusion of forskolin (10 and 30 μM) dose-dependently increased the cAMP levels to 417% and 1050% of the control group, respectively. Similarly, local infusion of NA (10 μM) increased the cAMP to the peak level of 168%. A 5-min tail pinch and a 10-min swim stress rapidly increased the NA and cAMP levels to 167% and 203% (NA) and 141% and 161% (cAMP), respectively. Infusion of galanin and CCK-8 (0.5 nmol, and 1.5 nmol/0.5 μl) dose-dependently increased NA to the peak levels of 191% and 179% and cAMP levels to 174% and 166%, respectively. The peak levels following infusions of vasopressin, substance P and neurokinin A were 91%, 135% and 86% for NA and 131%, 83% and 76% for cAMP, respectively. Infusions of anxiolytic-like peptides at highest concentrations significantly increased (NPY, 136%) or decreased (nociceptin, 71%; somatostatin, 86%) the NA levels, whereas neurotensin had no effect. The cAMP levels decreased to 86% (NPY, neurotensin), 78% (nociceptin), somatostatin infusion was without effect. The present findings confirmed a close correlation between the stress-induced increases in prefrontal cortical NA and cAMP levels, as well as, concurrent changes in NA and cAMP levels following infusions of galanin and CCK-8 (increased levels) and nociceptin/orphanin FQ (decreased levels). Infusions of other neuropeptides showed a more complex pattern of NA and cAMP responses.

译文

这项研究的目的是检查压力的影响以及局部注入的抗焦虑样神经肽galanin,CCK-8,加压素,p物质和神经激肽A以及抗焦虑样肽NPY,伤害肽/孤儿院FQ,生长抑素和神经降压素,通过微透析同时监测清醒大鼠内侧前额叶皮层去甲肾上腺素 (NA) 和cAMP外排的调节。通过新开发的方法确定cAMP的浓度,该方法基于cAMP用2-氯乙醛衍生化,然后通过HPLC进行荧光检测。局部输注福司可林 (10和30μm) 剂量依赖性地将cAMP水平分别增加到对照组的417% 和1050%。类似地,局部输注NA (10μm) 将cAMP增加到168% 的峰值水平。5分钟的尾巴捏和10分钟的游泳压力迅速将NA和cAMP水平分别增加到167% 和203% (NA) 以及141% 和161% (cAMP)。输注galanin和CCK-8 (0.5 nmol和1.5 nmol/0.5 μ l) 分别剂量依赖性地将NA增加到191% 和179% 的峰水平,将cAMP水平增加到174% 和166%。输注加压素,p物质和神经激肽A后的峰值水平分别为NA和131% 的91%,135% 和86%,cAMP的83% 和76%。最高浓度的抗焦虑样肽的输注显着增加 (NPY,136%) 或降低 (nociceptin,71%; 生长抑素,86%) NA水平,而神经降压素没有作用。cAMP水平降至86% (NPY,神经降压素),78% (伤害肽),生长抑素输注无作用。目前的发现证实了压力诱导的前额叶皮质NA和cAMP水平的增加,以及在注入galanin和CCK-8后NA和cAMP水平的同时变化 (水平升高) 和伤害肽/孤儿院蛋白FQ (降低水平)。其他神经肽的输注显示出NA和cAMP反应的更复杂模式。

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