Shanazz Khadijah, Nalloor Rebecca, Vazdarjanova Almira
VA Research Service, Charlie Norwood VA Medical Center, Augusta, GA, United States.
Department of Neuroscience and Regenerative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, United States.
Front Behav Neurosci. 2023 Sep 4;17:1231563. doi: 10.3389/fnbeh.2023.1231563. eCollection 2023.
Anxiety and anxiety-influenced disorders are sexually dimorphic with women being disproportionately affected compared to men. Given the increased prevalence in women and the documented differences in anxiety and trauma behavior between male and female rats this paper sought to examine the link between stress, anxiety, and fear learning and extinction in female rats. We tested the hypothesis that a mild stressor will induce short-and long-term increases in anxiety and produce long term effects on subsequent fear learning and extinction behavior.
We induced anxiety in female Sprague- Dawley rats with a short (3 min) exposure to a ball of cat hair infused with 150 μl of cat urine (mild stressor) that elicits innate fear but does not cause fear conditioning. The control group was exposed to fake cat hair. Anxiety was assessed in the Light-Dark Open Field (LDOF) or Elevated Plus Maze (EPM) before, immediately after and 4 days after stimulus exposure. Two weeks later, all animals were subject to Contextual Fear Conditioning (CFC) in the Shock Arm of a Y-maze, blocked off from the rest of the maze. Memory and fear extinction (learning of safety) was assessed in the following four days by placing each rat in one of the Safe Arms and measuring avoidance extinction (time spent and number of entries in the Shock Arm).
Cat hair exposure induced changes in anxiety-like behavior in the short-term that appeared resolved 4 days later. However, the cat-hair exposed rats had long-term (2 weeks) phenotypic changes expressed as altered exploratory behavior in an emotionally neutral novel place. Fear learning and extinction were not impaired. Yet, using avoidance extinction, we demonstrated that the phenotypic difference induced by the mild stressor could be documented and dissociated from learning and memory.
These findings demonstrate that the history of stress, even mild stress, has subtle long-term effects on behavior even when short-term anxiety appears resolved.
焦虑症及受焦虑影响的疾病存在性别差异，女性比男性受影响的比例更高。鉴于女性患病率上升以及雄性和雌性大鼠在焦虑和创伤行为方面已被记录的差异，本文旨在研究雌性大鼠应激、焦虑与恐惧学习及消退之间的联系。我们测试了这样一个假设：轻度应激源会在短期和长期内导致焦虑增加，并对随后的恐惧学习和消退行为产生长期影响。
我们通过让雌性斯普拉格-道利大鼠短时间（3分钟）接触一团浸有150微升猫尿的猫毛（轻度应激源）来诱发焦虑，这种应激源会引发先天恐惧但不会导致恐惧条件反射。对照组接触假猫毛。在刺激暴露前、暴露后立即以及暴露后4天，在明暗旷场（LDOF）或高架十字迷宫（EPM）中评估焦虑情况。两周后，所有动物在Y迷宫的电击臂中接受情境恐惧条件反射（CFC），该电击臂与迷宫的其余部分隔开。在接下来的四天里，通过将每只大鼠放入其中一个安全臂并测量回避消退情况（在电击臂中花费的时间和进入次数）来评估记忆和恐惧消退（对安全性的学习）。
接触猫毛在短期内引起了类似焦虑行为的变化，4天后这些变化似乎消失了。然而，接触猫毛的大鼠出现了长期（2周）的表型变化，表现为在情绪中性的新环境中探索行为改变。恐惧学习和消退并未受损。然而，通过回避消退，我们证明了轻度应激源引起的表型差异可以被记录下来，并与学习和记忆区分开来。
这些发现表明，即使短期焦虑似乎已消失，应激史，即使是轻度应激，也会对行为产生微妙的长期影响。
