Gamble-George Joyonna Carrie, Baldi Rita, Halladay Lindsay, Kocharian Adrina, Hartley Nolan, Silva Carolyn Grace, Roberts Holly, Haymer Andre, Marnett Lawrence J, Holmes Andrew, Patel Sachin
Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States.
Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States.
Elife. 2016 May 10;5:e14137. doi: 10.7554/eLife.14137.
Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show that traditional COX-2 inhibitors and a newly developed substrate-selective COX-2 inhibitor (SSCI) reduce a variety of stress-induced behavioral pathologies in mice. We found that these behavioral effects were associated with a dampening of neuronal excitability in the basolateral amygdala (BLA) ex vivo and in vivo, and were mediated by small-conductance calcium-activated potassium (SK) channel and CB1 cannabinoid receptor activation. Taken together, these data provide further support for the potential utility of SSCIs, as well as traditional COX-2 inhibitors, as novel treatment approaches for stress-related psychiatric disorders.
情绪和焦虑障碍是最常见的精神疾病，且会因压力而加剧。最近的研究表明，抑制环氧化酶-2（COX-2）可能代表一种针对包括焦虑症和重度抑郁症在内的情感障碍的新型治疗方法或增效策略。我们发现，传统的COX-2抑制剂和新开发的底物选择性COX-2抑制剂（SSCI）可减轻小鼠多种应激诱导的行为病理学症状。我们发现，这些行为效应与离体和体内基底外侧杏仁核（BLA）神经元兴奋性的抑制有关，并由小电导钙激活钾（SK）通道和CB1大麻素受体激活介导。综上所述，这些数据为SSCI以及传统COX-2抑制剂作为应激相关精神疾病的新型治疗方法的潜在效用提供了进一步支持。
