Department of Psychology, Sociology & Criminal Justice, Ohio Northern University, Ada, OH, USA.
Prog Neuropsychopharmacol Biol Psychiatry. 2013 Jul 1;44:1-16. doi: 10.1016/j.pnpbp.2013.01.001. Epub 2013 Jan 12.
Individuals exposed to life-threatening trauma are at risk for developing post-traumatic stress disorder (PTSD), a debilitating condition that involves persistent anxiety, intrusive memories and several physiological disturbances. Current pharmacotherapies for PTSD manage only a subset of these symptoms and typically have adverse side effects which limit their overall effectiveness. We evaluated the effectiveness of three different pharmacological agents to ameliorate a broad range of PTSD-like symptoms in our established predator-based animal model of PTSD. Adult male Sprague-Dawley rats were given 1-h cat exposures on two occasions that were separated by 10 days, in conjunction with chronic social instability. Beginning 24 h after the first cat exposure, rats received daily injections of amitriptyline, clonidine, tianeptine or vehicle. Three weeks after the second cat exposure, all rats underwent a battery of behavioral and physiological tests. The vehicle-treated, psychosocially stressed rats demonstrated a robust fear memory for the two cat exposures, as well as increased anxiety expressed on the elevated plus maze, an exaggerated startle response, elevated heart rate and blood pressure, reduced growth rate and increased adrenal gland weight, relative to the vehicle-treated, non-stressed (control) rats. Neither amitriptyline nor clonidine was effective at blocking the entire cluster of stress-induced sequelae, and each agent produced adverse side effects in control subjects. Only the antidepressant tianeptine completely blocked the effects of psychosocial stress on all of the physiological and behavioral measures that were examined. These findings illustrate the differential effectiveness of these three treatments to block components of PTSD-like symptoms in rats, and in particular, reveal the profile of tianeptine as the most effective of all three agents.
个体暴露于危及生命的创伤中，会有罹患创伤后应激障碍（PTSD）的风险，PTSD 是一种使人衰弱的病症，其涉及持续性焦虑、侵入性记忆和多种生理紊乱。目前用于 PTSD 的药物疗法仅能控制这些症状的一部分，且通常具有不良的副作用，限制了其整体疗效。我们评估了三种不同的药理学制剂在我们已建立的基于捕食者的 PTSD 动物模型中改善广泛的 PTSD 样症状的有效性。成年雄性 Sprague-Dawley 大鼠在 10 天的间隔内接受两次 1 小时的猫暴露，同时伴有慢性社会不稳定。第一次猫暴露后 24 小时，大鼠接受阿米替林、可乐定、噻奈普汀或载体的每日注射。第二次猫暴露后 3 周，所有大鼠接受一系列行为和生理测试。与载体处理的心理社会应激大鼠相比，接受载体处理的、经历过心理社会应激的大鼠对两次猫暴露表现出强烈的恐惧记忆，在高架十字迷宫上表现出更高的焦虑，惊跳反应过度，心率和血压升高，生长速度减慢，肾上腺重量增加。阿米替林或可乐定均不能有效阻断应激引起的所有后遗症，并且每种药物在对照大鼠中都产生了不良的副作用。只有抗抑郁药噻奈普汀完全阻断了心理社会应激对所有生理和行为测量的影响。这些发现说明了这三种治疗方法在阻断大鼠 PTSD 样症状的不同作用，并且特别揭示了噻奈普汀作为所有三种药物中最有效的药物的特征。
