A double-hit model of stress dysregulation in rats: implications for limbic corticosteroid receptors and anxious behavior under amitriptyline treatment
A double-hit model of stress dysregulation in rats: implications for limbic corticosteroid receptors and anxious behavior under amitriptyline treatment
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DOI：
10.3109/10253890.2014.910649
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发表时间：
2014-05-01
影响因子：
2.3
通讯作者：
Suarez, Marta M.
中科院分区：
文献类型：
--
作者：
Cotella, Evelin M.;Durando, Patricia E.;Suarez, Marta M.
早期生活中的逆境会导致成年后内分泌和行为对压力的不同反应。在我们的实验室里，我们评估了早期生活逆境的长期影响及其与成年期慢性压力的相互作用。我们提出这是对压力反应失调的脆弱性的一个模型。我们假设，在与焦虑样行为控制相关的边缘区域，接受两种方案的大鼠会表现出不同的皮质类固醇受体表达，以糖皮质激素受体（GR）或矿皮质激素受体（MR）免疫反应的神经元数量来衡量。我们还评估了阿米替林预防模型结果的效果。雄性Wistar大鼠在出生后3周内每天与母鼠分离4.5小时。从出生后第50天开始，对大鼠进行24 d的慢性可变应激（CVS）（5种应激源在一天的不同时间）。在应激方案中，大鼠每天给予阿米替林（10 mg/kg i.p）。MS在中央杏仁核诱发较低的MR表达，这被阿米替林逆转。此外，CVS增加海马区CA2的MR免疫反应性和增加焦虑行为；抗抑郁药阻止了这两种影响。当成年期MS合并CVS时，运动活动减少，阿米替林没有纠正作用。各组之间的差异效应可能意味着MS会促进另一种表型，这种表型在以后的生活中面对CVS（双重打击）时表达出来。
Adversity during early life can lead to diverging endocrine and behavioral responses to stress in adulthood. In our laboratory, we evaluated the long-term effects of early life adversity and its interaction with chronic stress during adulthood. We propose this as a model of vulnerability to dysregulation of the stress response. We hypothesized that rats subjected to both protocols would show differential expression of corticosteroid receptors measured as number of neurons immunoreactive for glucocorticoid receptors (GR) or mineralocorticoid receptors (MR), in limbic areas related to the control of anxiety-like behavior. We also evaluated the effect of amitriptyline expecting to prevent the outcomes of the model. Male Wistar rats were separated from the mother (MS) for 4.5 h every day for the first 3 weeks of life. From postnatal day 50, rats were subjected to chronic variable stress (CVS) during 24 d (five types of stressor at different times of day). During the stress protocol, the rats were administered amitriptyline (10 mg/kg i.p.) daily. MS evoked lower MR expression in the central amygdaloid nucleus and this was reversed by amitriptyline. Furthermore, CVS increased MR immunoreactivity in the hippocampal area CA2 and increased anxious behavior; both effects were prevented by the antidepressant. When MS was combined with CVS during adulthood, there was a reduction of locomotor activity, with no corrective effect of amitriptyline. The differential effects among groups could mean that MS would promote an alternative phenotype that is expressed when facing CVS (a double hit) later in life.