Zambello Erika, Jiménez-Vasquez Patricia A, El Khoury Aram, Mathé Aleksander A, Caberlotto Laura
Section of Pharmacology, Department of Medicine and Public Health, University of Verona, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2008 Apr 1;32(3):651-61. doi: 10.1016/j.pnpbp.2007.11.008. Epub 2007 Nov 17.
Preclinical and clinical evidence suggests that neuropeptides play a role in the pathophysiology of mood disorders. In the present study, we investigated the involvement of the peptides corticotropin-releasing hormone (CRH), neuropeptide Y (NPY) and nociceptin/orphanin FQ (N/OFQ) and of their receptors in the regulation of emotional behaviours. In situ hybridization experiments were performed in order to evaluate the mRNA expression levels of these neuropeptidergic systems in limbic and limbic-related brain regions of the Flinders Sensitive Line (FSL) rats, a putative genetic animal model of depression. The FSL and their controls, the Flinders Resistant Line (FRL) rats, were subjected to one hour acute restraint and the effects of the stress exposure, including possible strain specific changes on these neuropeptidergic systems, were studied. In basal conditions, no significant differences between FSL and FRL rats in the CRH mRNA expression were found, however an upregulation of the CRH mRNA hybridization signal was detected in the central amygdala of the stressed FRL, compared to the non stressed FRL rats, but not in the FSL, suggesting a hypoactive mechanism of response to stressful stimuli in the "depressed" FSL rats. Baseline levels of NPY and N/OFQ mRNA were lower in the FSL rats compared to the FRL in the dentate gyrus of hippocampus and in the medial amygdala, respectively. However, the exposure to stress induced a significant upregulation of the N/OFQ mRNA levels in the paraventricular thalamic nucleus, while in the same nucleus the N/OFQ receptor mRNA expression was higher in the FSL rats. In conclusion, selective alterations of the NPY and N/OFQ mRNA in limbic and limbic-related regions of the FSL rats, a putative animal model of depression, provide further support for the involvement of these neuropeptides in depressive disorders. Moreover, the lack of CRH activation following stress in the "depressed" FSL rats suggests a form of allostatic load, that could alter their interpretation of environmental stimuli and influence their behavioural response to stressful situations.
临床前和临床证据表明，神经肽在情绪障碍的病理生理学中起作用。在本研究中，我们调查了促肾上腺皮质激素释放激素（CRH）、神经肽Y（NPY）和孤啡肽/痛敏肽（N/OFQ）及其受体在情绪行为调节中的作用。进行了原位杂交实验，以评估这些神经肽能系统在弗林德斯敏感系（FSL）大鼠边缘和边缘相关脑区的mRNA表达水平，FSL大鼠是一种假定的抑郁症基因动物模型。FSL大鼠及其对照，即弗林德斯抗性系（FRL）大鼠，接受1小时的急性束缚，并研究应激暴露的影响，包括这些神经肽能系统可能的品系特异性变化。在基础条件下，FSL和FRL大鼠的CRH mRNA表达没有显著差异，然而，与未应激的FRL大鼠相比，应激的FRL大鼠中央杏仁核中检测到CRH mRNA杂交信号上调，但FSL大鼠中未检测到，这表明“抑郁”的FSL大鼠对应激刺激的反应机制不活跃。与FRL大鼠相比，FSL大鼠海马齿状回和内侧杏仁核中NPY和N/OFQ mRNA的基线水平分别较低。然而，应激暴露导致丘脑室旁核中N/OFQ mRNA水平显著上调，而在同一核中，FSL大鼠的N/OFQ受体mRNA表达较高。总之，在假定的抑郁症动物模型FSL大鼠的边缘和边缘相关区域中，NPY和N/OFQ mRNA的选择性改变为这些神经肽参与抑郁症提供了进一步的支持。此外，“抑郁”的FSL大鼠在应激后缺乏CRH激活，这表明一种形式的适应性负荷，可能会改变它们对环境刺激的解释，并影响它们对应激情况的行为反应。
