Department of Psychology and Program in Neuroscience, Hamilton College, Clinton, NY 13323, United States.
Department of Psychology, University of South Carolina Upstate, Spartanburg, SC 29303, United States.
Physiol Behav. 2019 Jan 1;198:120-133. doi: 10.1016/j.physbeh.2018.10.012. Epub 2018 Oct 16.
Many people will experience at least one traumatic event in their lifetime, with up to 20% developing Post-Traumatic Stress Disorder (PTSD) or PTSD-like symptoms. In addition, the likelihood that females will develop PTSD after trauma is more than twice that of males. Despite its prevalence, current treatment strategies for trauma victims are limited and substantial portions of affected individuals remain resistant to treatment, suggesting that additional interventions are necessary. Using an animal model of traumatic stress, the present studies tested the hypothesis that either voluntary exercise and/or administration of the adrenergic beta-receptor antagonist propranolol, would ameliorate stress-related maladaptive behaviors. In Study 1 four groups of female rats were exposed to a sequence of stressors that included anesthesia, restraint, forced swim, exposure to predator scent and fear conditioning. Rats then underwent re-exposure sessions in which stress-related conditioned stimuli were presented. In addition to re-exposure, stressed rats were treated with propranolol (10 mg/kg) and/or given the opportunity to engage in voluntary wheel running intermittently for 4 weeks. Stress-associated maladaptive behavior was assessed using the elevated plus and open field mazes and fear memory tests. Cognitive ability was assessed using a novel odor recognition task. A main effect of exercise on behaviors related to anxiety and resilience was observed, but neither a main effect of propranolol nor a synergistic effect of propranolol and exercise were observed. Neither stress induction nor treatment influenced recognition memory. In contrast, in Study 2 in which the timing and dosage of propranolol (0.25-2.0 mg/kg), and the number and timing of re-exposure sessions were adjusted, propranolol produced both a reduction in anxiety-like behaviors as well as resilience to a subsequent stressor. These results are consistent with the notion that combining re-exposure therapy with additional interventions is beneficial for female trauma victims. Furthermore, the findings support the view that in pre-clinical models, voluntary exercise, which bolsters hippocampal function and propranolol, which affects amygdala-dependent memory reconsolidation and peripheral noradrenergic signaling, can ameliorate stress-related symptoms.
许多人在一生中都会经历至少一次创伤事件，其中多达 20%的人会发展出创伤后应激障碍（PTSD）或类似 PTSD 的症状。此外，女性在创伤后发展出 PTSD 的可能性是男性的两倍多。尽管 PTSD 很常见，但目前针对创伤受害者的治疗策略有限，大量受影响的个体仍然对治疗有抵抗力，这表明需要额外的干预措施。本研究使用创伤应激的动物模型，检验了以下假设：即自愿运动和/或使用肾上腺素能β受体拮抗剂普萘洛尔（propranolol），可以改善与应激相关的适应不良行为。在研究 1 中，四组雌性大鼠接受了一系列应激源的暴露，包括麻醉、束缚、强迫游泳、暴露于捕食者气味和恐惧条件反射。然后，大鼠进行了重新暴露，其中呈现与应激相关的条件刺激。除了重新暴露，应激大鼠还接受了普萘洛尔（10mg/kg）治疗，或有机会间歇性地进行 4 周的自愿轮跑。使用高架十字迷宫和开阔场迷宫以及恐惧记忆测试评估与应激相关的适应不良行为。使用新的气味识别任务评估认知能力。运动对与焦虑和恢复力相关的行为有显著影响，但普萘洛尔的主要作用或普萘洛尔与运动的协同作用都没有观察到。应激诱导或治疗都不影响识别记忆。相比之下，在研究 2 中，调整了普萘洛尔的时间和剂量（0.25-2.0mg/kg），以及重新暴露的次数和时间，普萘洛尔既能减少焦虑样行为，又能恢复对后续应激源的抵抗力。这些结果与以下观点一致，即重新暴露治疗与其他干预措施相结合，对女性创伤受害者有益。此外，这些发现支持了以下观点，即在临床前模型中，自愿运动可以增强海马功能，普萘洛尔可以影响杏仁核依赖的记忆再巩固和外周去甲肾上腺素能信号，从而改善与应激相关的症状。
