Chronic stress increases the probability of receiving an anxiety, depression, or chronic illness diagnosis. Pharmacological interventions that reduce the behavioral and physiological effects of chronic stress in animal models may represent novel approaches for the treatment of stress-related psychiatric disorders. Here, we examined the effects of cyclooxygenase-2 (COX-2) inhibition on anxiety-like behaviors and amygdala glutamatergic signaling after chronic non-invasive oral corticosterone (CORT) administration in mice. Treatment with the highly selective COX-2 inhibitor Lumiracoxib (LMX) reversed anxiety-like behavior induced by chronic CORT. Specifically, acute and repeated administration of LMX 5 mg kg⁻¹ reduced chronic CORT-induced anxiety-like behavior measured using the elevated-plus maze, elevated-zero maze, and light-dark box tests. In contrast, LMX did not affect anxiety-like behaviors in naïve mice. Ex vivo electrophysiology studies revealed that repeated LMX treatment normalized chronic CORT-induced increases in spontaneous excitatory glutamatergic currents recorded from anterior, but not posterior, basolateral amygdala neurons. These data indicate COX-2 inhibition can reverse chronic CORT-induced increases in anxiety-like behaviors and amygdala glutamatergic signaling, and support further clinical investigation of selective COX-2 inhibitors for the treatment of affective and stress-related psychiatric disorders.

慢性压力会增加接受焦虑症，抑郁症或慢性病诊断的可能性。降低动物模型中慢性应激的行为和生理影响的药理干预措施可能代表了治疗与应激有关的精神疾病的新方法。在这里，我们检查了对小鼠进行慢性非侵入性口服皮质酮（CORT）给药后环氧合酶2（COX-2）抑制作用对焦虑样行为和杏仁核谷氨酸能信号传导的影响。用高度选择性的COX-2抑制剂Lumiracoxib（LMX）治疗可逆转慢性CORT诱发的焦虑样行为。具体而言，急性和反复给药LMX 5 mg kg ^-1使用高架迷宫，高架零迷宫和浅色暗箱测试所测得的CRT减少的慢性CORT诱发的焦虑样行为。相比之下，LMX不会影响幼稚小鼠的焦虑样行为。体外电生理学研究表明，反复进行LMX治疗可以使慢性CORT诱发的自前基底基底杏仁核神经元而非后基底杏仁核神经元记录的自发性兴奋性谷氨酸能电流增加。这些数据表明，COX-2抑制作用可以逆转慢性CORT诱导的焦虑样行为和杏仁核谷氨酸能信号转导的增加，并支持选择性COX-2抑制剂用于治疗情感性和压力性精神病的进一步临床研究。