Clinical and experimental studies have shown that the activation of corticotropin-releasing hormone (CRH) and noradrenergic systems mediate stress-induced anxiety. Repeated immobilization stress (RIS) has been shown to induce long-lasting anxiety behavior and changes in noradrenaline turnover. The present work was aimed at studying the effect of RIS on the in situ expression of CRH-LI in the central extended amygdala and paraventricular nucleus of the hypothalamus (PVN). Our results showed that RIS for 15 days induces a significant increase of CRH-LI expression in the central extended amygdala. The increase in CRH-LI expression in the central extended amygdala was sustained even after a 25-day stress-free period. The concomitant administration of desipramine (DMI), a specific noradrenaline uptake inhibitor, fully prevented the RIS-induced increase in CRH expression. RIS also induced an increase of CRH-LI expression in the PVN that was prevented by the concomitant DMI administration. In contrast to the sustained effect observed in the central extended amygdala, the RIS-induced increase of CRH-LI expression in the PVN was nonlasting. DMI administration also prevented the RIS-induced increase of adrenal gland weight. The present findings showing that RIS induces a sustained increase of CRH expression in the central extended amygdala suggest that the repeated activation of CRH neurons and CRH receptors in the central extended amygdala may underlie the long-lasting anxiety behavior induced by RIS. Further studies should address the mechanisms involved in the effect of DMI and its eventual relevance in the therapeutic actions of DMI.

译文

:临床和实验研究表明,促肾上腺皮质激素释放激素(CRH)和去甲肾上腺素能系统的激活介导了压力诱发的焦虑。反复的固定应激(RIS)已显示出引起长期的焦虑行为和去甲肾上腺素周转率的变化。目前的工作旨在研究RIS对下丘脑中央延伸杏仁核和室旁核(PVN)中CRH-LI原位表达的影响。我们的结果表明,RIS持续15天会导致中央中央杏仁核中CRH-LI表达的显着增加。即使在25天的无压力期后,中央延伸杏仁核中CRH-LI表达的增加仍然持续。伴随给药地昔帕明(DMI)(一种特定的去甲肾上腺素摄取抑制剂)的同时给药,完全可以防止RIS引起的CRH表达增加。 RIS还诱导了PVN中CRH-LI表达的增加,这可以通过同时给予DMI来预防。与在中央延伸杏仁核中观察到的持续作用相反,RIS诱导的PVN中CRH-LI表达的增加是持久的。 DMI管理还可以防止RIS引起的肾上腺重量增加。目前的发现表明,RIS诱导中央延伸杏仁核中CRH表达的持续增加,表明中央延伸杏仁核中CRH神经元和CRH受体的重复激活可能是RIS诱导的长期焦虑行为的基础。进一步的研究应解决DMI的作用及其最终与DMI的治疗作用相关的机制。

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