Alterations in stress-associated behaviors and neurochemical markers in adult rats after neonatal short-lasting local inflammatory insult
Alterations in stress-associated behaviors and neurochemical markers in adult rats after neonatal short-lasting local inflammatory insult
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DOI：
10.1016/j.neuroscience.2004.11.039
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发表时间：
2005-01-01
期刊：
影响因子：
3.3
通讯作者：
Lidow, MS
中科院分区：
文献类型：
--
作者：
Anseloni, VCZ;He, F;Lidow, MS
最近，人们对新生儿疼痛的长期后果越来越感兴趣，因为现代新生儿重症监护病房通常采用的手术会引起相当大的疼痛，并可能伴随持续数小时甚至数天的局部炎症和痛觉过敏。为了解决这个问题，我们建立了一个大鼠模型，通过向后爪足底表面单次注射0.25%的卡拉胶（CAR）产生短期（< 2天）早期局部炎症损伤。在此之前，我们证明，在出生后第一周内接受这种治疗的大鼠长大成人后，对急性疼痛的反应性整体降低。在这里，我们报告说，这些动物也表现出与对压力的情绪反应降低相关的低焦虑特征。这一结论是基于以下观察得出的：(a)我们模型中的大鼠在升高的+迷宫中表现出较低的焦虑；(b)在强迫游泳实验中，大鼠表现出较强的应激应对能力相关行为特征；(c)这些动物降低了基础水平和应激诱导的血浆中与应激相关的神经内分泌标志物，如促肾上腺皮质激素释放因子、加压素和促肾上腺皮质激素。此外，我们在动物模型中使用DNA微阵列和实时逆转录酶聚合酶链反应来分析中脑导水管周围灰质（PAG，一个参与应激和疼痛调节的区域）基因表达的长期变化。在受影响的基因中，血清素能受体的表现尤为明显。具体来说，我们检测到5-HT1A、5-HT1D、5-HT2A、5-HT2C和5-HT4受体的表达增加。已知其中一些受体参与PAG的抗焦虑和镇痛活性。最后，为了确定新生儿炎症性损伤是否会导致产妇护理水平升高，这可能在我们的模型中所见的长期行为改变中发挥作用，我们在CAR注射后3天检查了产妇的行为。事实上，我们观察到，在炎症发生时，母鼠对幼崽的关注大幅增加，但这种增加并不是没有代价的：之后一段时间内母鼠对幼崽的严重忽视。(c) 2005 IBRO。Elsevier Ltd.出版。版权所有。
Recently, there has been a growing interest in long-term consequences of neonatal pain because modern neonatal intensive care units routinely employ procedures that cause considerable pain and may be followed by local inflammation and hyperalgesia lasting for several hours or even days. To address this question, we developed a rat model of short lasting (< 2 days) early local inflammatory insult produced by a single injection of 0.25% carrageenan (CAR) into the plantar surface of a hindpaw. Previously, we demonstrated that rats receiving this treatment within the first week after birth grow into adults with a global reduction in responsiveness to acute pain. Here, we report that these animals also manifest a low anxiety trait associated with reduced emotional responsiveness to stress. This conclusion is based in the following observations: (a) rats in our model display reduced anxiety on an elevated plus-maze; (b) in the forced swim test, these rats exhibit behavioral characteristics associated with stronger ability for stress coping; and (c) these animals have reduced basal and stress-induced plasma levels of such stress-related neuroendocrine markers as corticotropin-releasing factor, vasopressin, and adrenocorticotrophic hormone. In addition, we used DNA microarray and real-time reverse-transcriptase polymerase chain reaction to profile long-term changes in gene expression in the midbrain periaqueductal gray (PAG; a region involved in both stress and pain modulation) in our animal model. Among the affected genes, serotonergic receptors were particularly well represented. Specifically, we detected increase in the expression of 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C and 5-HT4 receptors. Several of these receptors are known to be involved in the anxiolytic and analgesic activity of the PAG. Finally, to determine whether neonatal inflammatory insult induces elevation in maternal care, which may play a role in generating long-term behavioral alterations seen in our model, we examined maternal behavior for 3 days following CAR injection. Indeed, we observed a substantial increase in maternal attention to the pups at the time of inflammation, but this increase was not without its cost: a period of significant maternal neglect afterward. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.