Stress is a major risk factor for the development and exacerbation of mood and anxiety disorders, and recent studies have suggested inflammatory contributions to the pathogenesis of depression. Interestingly, pharmacological inhibition of cyclooxygenase-2 (COX-2) has shown promise in the treatment of affective disorders in small scale clinical studies; however, the mechanisms by which COX-2 inhibition affects behavioral domains relevant to affective disorders are not well understood. Here, we examined the effects of pharmacological inhibition of COX-2 with the highly selective inhibitor Lumiracoxib (LMX) on anxiety-like behavior and in vivo basolateral amygdala (BLA) neural activity in response to acute restraint stress exposure. In male mice, pretreatment with LMX prevented the increase in BLA calcium transients induced by restraint stress and prevented anxiogenic behavior seen after restraint stress exposure. Specifically, acute injection of LMX 5mg kg-1 reduced anxiety-like behavior in the light-dark box (LD) and elevated-zero maze (EZM). In addition, in vivo fiber photometry studies showed that acute stress increased calcium transients and the predicted action potential frequency of BLA neurons, which was also normalized by acute LMX pretreatment. These findings indicate pharmacological inhibition of COX-2 can prevent acute stress-induced increase in BLA cellular activity and anxiety-like behavior and provides insights into the neural mechanisms by which COX-2 inhibition could affect anxiety domain symptoms in patients with affective disorders.

中文翻译：

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环氧合酶 2 抑制可防止压力诱导的杏仁核激活和焦虑样行为

压力是情绪和焦虑障碍发展和恶化的主要风险因素，最近的研究表明炎症对抑郁症的发病机制有贡献。有趣的是，在小规模临床研究中，环氧合酶 2 (COX-2) 的药理学抑制已显示出治疗情感障碍的前景。然而，COX-2 抑制影响与情感障碍相关的行为域的机制尚不清楚。在这里，我们研究了高选择性抑制剂 Lumiracoxib (LMX) 对 COX-2 的药理学抑制作用对急性约束应激暴露的焦虑样行为和体内基底外侧杏仁核 (BLA) 神经活动的影响。在雄性小鼠中，用 LMX 预处理可防止由约束应激引起的 BLA 钙瞬变的增加，并防止在约束应激暴露后出现的焦虑行为。具体而言，急性注射 LMX 5mg kg-1 可减少明暗箱 (LD) 和高架零迷宫 (EZM) 中的焦虑样行为。此外，体内纤维光度学研究表明，急性应激增加了钙瞬变和 BLA 神经元的预测动作电位频率，这也通过急性 LMX 预处理而正常化。这些发现表明，COX-2 的药理学抑制可以防止急性应激诱导的 BLA 细胞活性增加和焦虑样行为，并提供对 COX-2 抑制可能影响情感障碍患者焦虑域症状的神经机制的见解。