Post Ryan J, Dahlborg Kaitlyn M, O'Loughlin Lauren E, Bloom Christopher M
Providence College, 1 Cunningham Sq., Providence, RI 02918, USA.
Providence College, 1 Cunningham Sq., Providence, RI 02918, USA.
Physiol Behav. 2014 May 28;131:57-61. doi: 10.1016/j.physbeh.2014.04.009. Epub 2014 Apr 13.
Clinical researchers have tracked patients with early life trauma and noted generalized anxiety disorder, unipolar depression, and risk-taking behaviors developing in late adolescence and into early adulthood. Animal models provide an opportunity to investigate the neural and developmental processes that underlie the relationship between early stress and later abnormal behavior. The present model used repeated exposure to 2,3,5-trimethyl-3-thiazoline (TMT), a component of fox feces, as an unconditioned fear-eliciting stimulus in order to induce stress in juvenile rats aged postnatal day (PND) 23 through 27. After further physical maturation characteristic of the adolescent stage (PND 42), animals were tested using an elevated plus maze (EPM) for anxiety and plantar test (Hargreaves method) for pain to assess any lingering effects of the juvenile stress. To assess how an additional stress later in life affects anxiety and pain nociception, PND 43 rats were exposed to inescapable shock (0.8mA) and again tested on EPM and plantar test. A final testing period was conducted in the adult (PND 63) rats to assess resulting changes in adult behaviors. TMT-exposed rats were significantly more anxious in adolescence than controls, but this difference disappeared after exposure to the secondary stressor. In adulthood, but not in adolescence, TMT-exposed rats demonstrated lower pain sensitivity than controls. These results suggest that early life stress can play a significant role in later anxiety and pain nociception, and offer insight into the development and manifestation of anxiety- and trauma-related disorders.
临床研究人员追踪了有早期生活创伤的患者,并注意到在青春期后期及成年早期出现了广泛性焦虑症、单相抑郁症和冒险行为。动物模型为研究早期应激与后期异常行为之间关系背后的神经和发育过程提供了机会。本模型使用反复暴露于狐狸粪便成分2,3,5-三甲基-3-噻唑啉(TMT)作为无条件恐惧诱发刺激,以诱导出生后第23至27天的幼年大鼠产生应激。在经历青春期进一步的身体成熟特征(出生后第42天)后,使用高架十字迷宫(EPM)测试动物的焦虑情况,并用足底测试(哈格里夫斯方法)测试疼痛情况,以评估幼年应激的任何残留影响。为了评估生命后期的额外应激如何影响焦虑和疼痛感受,对出生后第43天的大鼠施加不可逃避的电击(0.8mA),并再次在EPM和足底测试中进行测试。在成年(出生后第63天)大鼠中进行了最后一个测试阶段,以评估成年行为产生的变化。暴露于TMT的大鼠在青春期比对照组明显更焦虑,但在暴露于二次应激源后这种差异消失了。在成年期而非青春期,暴露于TMT的大鼠表现出比对照组更低的疼痛敏感性。这些结果表明,早期生活应激可能在后期焦虑和疼痛感受中发挥重要作用,并为焦虑和创伤相关障碍的发展和表现提供了见解。