Abstract:
Post-traumatic stress disorder (PTSD) is a debilitating disorder characterized by excessive fear, hypervigilance, and avoidance of thoughts, situations or reminders of the trauma. Among these symptoms, relatively little is known about the etiology of pathological avoidance. Here we sought to determine whether acute stress influences avoidant behavior in adult male and female rats. We used a stress procedure (unsignaled footshock) that is known to induce long-term sensitization of fear and potentiate aversive learning. Rats were submitted to the stress procedure and, one week later, underwent two-way signaled active avoidance conditioning (SAA). In this task, rats learn to prevent an aversive outcome (shock) by performing a shuttling response when exposed to a warning signal (tone). We found that acute stress significantly enhanced SAA acquisition rate in females, but not males. Female rats exhibited significantly greater avoidance responding on the first day of training relative to controls, reaching similar levels of performance by the second day. Males that underwent the stress procedure showed similar rates of acquisition to controls but exhibited resistance to extinction. This was manifest as both elevated avoidance and intertrial responding across extinction days relative to non-stressed controls, an effect that was not observed in females. In a second experiment, acute stress sensitized footshock unconditioned responses in males, not females. However, males and females exhibited similar levels of stress-enhanced fear learning (SEFL), which was expressed as sensitized freezing to a shock-paired context. Together, these results reveal that acute stress facilitates SAA performance in both male and female rats, though the nature of this effect is different in the two sexes. We did not observe sex differences in SEFL, suggesting that the stress-induced sex difference in performance was selective for instrumental avoidance. Future work will elucidate the neurobiological mechanisms underlying the differential effect of stress on instrumental avoidance in male and female rats.
摘要:
创伤后应激障碍(PTSD)是一种使人衰弱的障碍,其特征是过度恐惧,高度警惕,和避免思想,创伤的情况或提醒。在这些症状中,对病理性回避的病因知之甚少。在这里,我们试图确定急性压力是否会影响成年雄性和雌性大鼠的回避行为。我们使用了一种压力程序(无信号的脚部电击),该程序已知会引起长期的恐惧敏感性并增强厌恶学习。大鼠接受了应激程序,一周后,接受了双向信号主动回避条件(SAA)。在这项任务中,当暴露于警告信号(音调)时,大鼠通过执行穿梭反应来学习防止令人厌恶的结果(电击)。我们发现急性应激显著提高了女性的SAA获得率,但不是男性。与对照组相比,雌性大鼠在训练的第一天表现出明显更大的回避反应。在第二天达到类似的性能水平。经历应激程序的雄性表现出与对照组相似的获取率,但表现出对灭绝的抵抗力。这表现为相对于非应激对照,在整个灭绝日的回避和试验间反应都提高了。在女性中没有观察到的效果。在第二个实验中,男性急性应激致敏性足休克非条件反应,不是女性。然而,男性和女性表现出相似的压力增强恐惧学习水平(SEFL),这被表示为对休克配对背景敏感的冻结。一起,这些结果表明,急性应激促进SAA在雄性和雌性大鼠的表现,虽然这种影响的性质在两种性别中是不同的。我们没有观察到SEFL的性别差异,这表明压力引起的性别差异对工具回避是有选择性的。未来的工作将阐明在雄性和雌性大鼠中压力对工具回避的不同影响的神经生物学机制。