Centre for Psychiatric Research, Aarhus University Hospital Risskov, Skovagervej 2, 8240 Risskov, Denmark.
Brain Res. 2010 Mar 12;1320:106-13. doi: 10.1016/j.brainres.2010.01.008. Epub 2010 Jan 11.
The origin of adult behavior and the possible pathogenesis of psychiatric disorders remain elusive, but extensive research indicates that interaction of genes and environment play a crucial role for adult phenotype. Differences in susceptibility may arise by earlier experiences and genomic variables, either alone or in combination. The acoustic startle response (ASR) has been shown to be altered in patients with several psychiatric diseases, a change that could result from a persistent sensitization caused by chronic arousal secondary to a traumatic incident. The current work hypothesized that a single aversive procedure would induce long-term hyperactivity in the HPA-axis of rats that had become vulnerable by prenatal stress, and thereby change reactivity in the ASR. Prenatal stress was achieved by maternal gestational exposure to Chronic Mild Stress (CMS). At age 3 months, the offspring were blood sampled by a stressful procedure, and subsequently tested in the acoustic startle paradigm. Prenatal CMS strongly reduced prepulse inhibition (PPI) whereas postnatal blood sampling under restraint generally increased PPI. Our data demonstrate interplay between pre- and postnatal stressful events, but also that this interaction is complex and could influence the interplay between PPI and basal startle. Our results suggest that circumstances dating back to early development may have implications for adult life behavior, and based on this we propose a new theory of a threshold in the induction of a stress response in the ASR test, which influences whether the PPI or basal startle response will be affected.
成人行为的起源和精神障碍的可能发病机制仍然难以捉摸,但广泛的研究表明,基因和环境的相互作用对成人表型起着至关重要的作用。易感性的差异可能是由于早期经历和基因组变量单独或组合引起的。几项精神疾病患者的听觉惊吓反应(ASR)已被证明发生了改变,这种变化可能是由于创伤事件引起的慢性唤醒导致的持续敏感化所致。目前的工作假设,单次厌恶程序会导致产前应激使大鼠易患的 HPA 轴长期过度活跃,从而改变 ASR 的反应性。通过母体妊娠期暴露于慢性轻度应激(CMS)来实现产前应激。在 3 个月大时,通过有压力的程序对后代进行采血,然后在听觉惊吓范式中进行测试。产前 CMS 强烈降低了预脉冲抑制(PPI),而在束缚下进行的产后采血通常会增加 PPI。我们的数据表明,产前和产后应激事件之间存在相互作用,但这种相互作用很复杂,可能会影响 PPI 和基础惊吓之间的相互作用。我们的结果表明,早在发育早期的情况可能对成年后的行为产生影响,基于这一点,我们提出了一个关于 ASR 测试中应激反应诱导的阈值的新理论,该理论影响 PPI 或基础惊吓反应是否会受到影响。