Foilb Allison R, Christianson John P
Department of Psychology, Boston College, Chestnut Hill, MA 02467, USA.
Department of Psychology, Boston College, Chestnut Hill, MA 02467, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2016 Feb 4;65:78-84. doi: 10.1016/j.pnpbp.2015.08.017. Epub 2015 Sep 4.
The capacity to discriminate between safety and danger is fundamental for survival, but is disrupted in individuals with posttraumatic stress disorder (PTSD). Acute stressors cause a release of serotonin (5-HT) in the forebrain, which is one mechanism for enhanced fear and anxiety; these effects are mediated by the 5-HT2Creceptor. Using a fear discrimination paradigm where a danger signal conditioned stimulus (CS+) co-terminates with a mild footshock and a safety signal (CS-) indicates the absence of shock, we demonstrate that danger/safety discrimination and fear inhibition develop over the course of 4 daily conditioning sessions. Systemic administration of the 5-HT2Creceptor antagonist SB 242084 (0.25 or 1.0mg/kg) prior to conditioning reduced behavioral freezing during conditioning, and improved learning and subsequent inhibition of fear by the safety signal. Discrimination was apparent in the first recall test, and discrimination during training was evident after 3days of conditioning versus 5days in the vehicle treated controls. These results suggest a novel therapeutic use for 5-HT2Creceptor antagonists to improve learning under stressful circumstances. Potential anatomical loci for 5-HT2Creceptor modulation of fear discrimination learning and cognitive performance enhancement are discussed.
John P. Christianson and Allison R. Foilb, the authors, verify that animal research was carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23) and all procedures involving animals were reviewed and approved by the Boston College Animal Care and Use Committee. All efforts were made to limit the number of animals used and their suffering.
区分安全与危险的能力是生存的基础，但在创伤后应激障碍（PTSD）患者中会受到破坏。急性应激源会导致前脑中血清素（5-HT）的释放，这是恐惧和焦虑增强的一种机制；这些效应由5-HT2C受体介导。使用一种恐惧辨别范式，其中危险信号条件刺激（CS+）与轻度足部电击同时终止，而安全信号（CS-）表示无电击，我们证明危险/安全辨别和恐惧抑制在4天的每日条件训练过程中逐渐发展。在条件训练前全身给予5-HT2C受体拮抗剂SB 242084（0.25或1.0mg/kg）可减少条件训练期间的行为僵住，并改善学习以及随后安全信号对恐惧的抑制。在第一次回忆测试中辨别就很明显，与接受载体处理的对照组在5天的条件训练相比，在3天的条件训练后训练期间的辨别就很明显。这些结果表明5-HT2C受体拮抗剂在改善应激情况下的学习方面有新的治疗用途。讨论了5-HT2C受体调节恐惧辨别学习和增强认知表现的潜在解剖位点。
作者约翰·P·克里斯蒂安森和艾莉森·R·福伊尔布证实，动物研究是按照美国国立卫生研究院《实验动物饲养与使用指南》（NIH出版物第80 - 23号）进行的，所有涉及动物的程序均经波士顿学院动物护理与使用委员会审查和批准。已尽一切努力限制所用动物的数量及其痛苦。
