The effect of lateral septum corticotropin-releasing factor receptor 2 activation on anxiety is modulated by stress
The effect of lateral septum corticotropin-releasing factor receptor 2 activation on anxiety is modulated by stress
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DOI：
10.1523/jneurosci.1494-06.2006
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发表时间：
2006-09-06
影响因子：
5.3
通讯作者：
Markou, Athina
中科院分区：
文献类型：
--
作者：
Henry, Brook;Vale, Wylie;Markou, Athina
促肾上腺皮质激素释放因子（CRF）是一种由41个氨基酸组成的多肽，可介导应激时的内分泌、自主神经和行为反应。尽管CRF 1受体似乎有助于与压力相关的焦虑，但CRF 2受体的作用仍不清楚，可能取决于药物剂量，大脑位置或测试环境。涉及选择性CRF 2受体激动剂或拮抗剂治疗的结果以及CRF 2受体敲除小鼠的行为表明CRF 2受体活化的致焦虑和抗焦虑作用。本研究验证了CRF 2受体激活对焦虑的影响取决于动物的应激水平的假设。选择性CRF 2受体激动剂urocortin 2在低或高应力（30分钟的固定）测试条件下注入小鼠的侧隔，然后在明暗箱，开放领域，和新对象测试中的行为进行了评估。在低压力环境中，240 pmol的隔尿皮质素2增加焦虑，但较低剂量（0.48、4.8和48 pmol）没有一致的效果。然而，在高应激条件下，与对照相比，48 pmol的中隔尿皮质素2显著增加了亮-暗箱中野生型而非CRF 2受体敲除小鼠的焦虑。隔室给药的相对选择性CRF 2拮抗剂astressin-2B，而不是CRF 1选择性拮抗剂antalarmin，阻断了urocortin 2的抗焦虑作用。将Urocortin 2注入内侧隔或侧脑室不影响焦虑测量。这些结果表明，隔CRF 2受体激活对焦虑的影响依赖于应激水平。
Corticotropin-releasing factor (CRF), a 41 amino acid peptide, mediates endocrine, autonomic, and behavioral responses to stress. Whereas the CRF1 receptor appears to contribute to anxiety associated with stress, the role of the CRF2 receptor remains unclear and may depend on drug dose, brain location, or testing environment. Results involving treatments with selective CRF2 receptor agonists or antagonists and the behavior of CRF2 receptor knock-out mice suggest both anxiogenic and anxiolytic effects of CRF2 receptor activation. The present study tested the hypothesis that the effect of CRF2 receptor activation on anxiety depends on the stress level of the animal. The selective CRF2 receptor agonist urocortin 2 was infused into the lateral septum of mice under low- or high-stress (30 min of immobilization) testing conditions, and then behavior in the light-dark box, open-field, and novel-object tests was assessed. In the low- stress environment, 240 pmol of septal urocortin 2 increased anxiety, but lower doses (0.48, 4.8, and 48 pmol) did not have consistent effects. However, in the high-stress condition, 48 pmol of septal urocortin 2 significantly increased anxiety compared with control in wild-type but not CRF2 receptor knock- out mice in the light-dark box. Septal administration of the relatively selective CRF2 antagonist astressin-2B, but not the CRF1-selective antagonist antalarmin, blocked the anxiogenic effects of urocortin 2. Urocortin 2 infusion into the medial septum or lateral ventricle did not affect anxiety measures. These results indicate that the effect of septal CRF2 receptor activation on anxiety is dependent on stress level.