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首页> 外文学位 >The Effects of Corticotropin-Releasing Factor and Restraint Stress on Prepulse Inhibition of the Acoustic Startle Response in Rats.
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The Effects of Corticotropin-Releasing Factor and Restraint Stress on Prepulse Inhibition of the Acoustic Startle Response in Rats.

机译：促肾上腺皮质激素释放因子和束缚应激对大鼠惊吓反应的脉冲抑制的影响。

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摘要

Stress can be broadly defined as "an actual or anticipated disruption of homeostasis or an anticipated threat to well-being" (Ulrich-Lai and Herman 2009). When a person develops maladaptive stress responses or coping strategies, the effects of stress can become deleterious and pathological conditions can arise, including psychiatric disorders. For example, exposure to stressful events can exacerbate symptoms in people suffering from schizophrenia or can trigger the onset of anxiety disorders such as post-traumatic stress disorder (PTSD). Due to the complex neurobiology of schizophrenia and PTSD, we focused our research on one particular aspect, or endophenotype, known to be aberrant in these disorders. Decreased prepulse inhibition (PPI) of the acoustic startle response is the endophenotype that we used to investigate processes that contribute to stress-related psychiatric disorders. PPI is the reduction in startle amplitude caused by brief presentation of a non-startling acoustic stimulus shortly prior to a startling stimulus, and is recognized as a simple operational measure of sensorimotor gating. Since PPI can be assessed in both humans and rodents using nearly identical parameters, it a useful tool for investigating human information processing deficits using animal models.;We proposed that corticotropin-releasing factor (CRF) contributes to the reduced PPI observed in people diagnosed with stress-related psychiatric disorders. Considerable evidence supports this hypothesis. First, CRF is one of the most important neurotransmitters involved in behavioral components of the stress response. Second, central infusion of CRF decreases PPI in rodents. Third, CRF acts via CRF receptors located in regions of the brain that modulate PPI. Fourth, the brain regions that modulate PPI and express CRF receptors are known to be abnormal in schizophrenia and PTSD.;Although central infusion of CRF decreases PPI in rodents, it is not known whether CRF decreases PPI indirectly via its effects on other neurotransmitters, such as serotonin, or whether stress modulates PPI via the endogenous CRF system in the same manner that exogenous CRF modulates PPI. As a result, the ultimate goal of this dissertation is to explore these topics and to further our understanding of the mechanisms by which CRF and stress affect sensorimotor gating.
机译：压力可以广义地定义为“稳态的实际或预期破坏或对幸福的预期威胁”（Ulrich-Lai和Herman 2009）。当一个人发展出适应不良的压力反应或应对策略时，压力的影响会变得有害，并可能引起包括精神疾病在内的病理状况。例如，暴露于压力事件会加剧精神分裂症患者的症状，或引发焦虑症（如创伤后应激障碍（PTSD））的发作。由于精神分裂症和PTSD的复杂神经生物学，我们将研究重点放在已知在这些疾病中异常的一个特定方面或内表型。声音惊吓反应的减少的脉冲前抑制（PPI）是我们用来调查导致与压力有关的精神疾病的过程的内表型。 PPI是由于在惊吓刺激之前不久出现非惊吓声刺激而引起的惊吓幅度降低，并且被认为是感觉运动门控的一种简单操作措施。由于PPI可以使用几乎相同的参数在人类和啮齿动物中进行评估，因此它是使用动物模型研究人类信息处理缺陷的有用工具。;我们提出促肾上腺皮质激素释放因子（CRF）有助于在确诊患有PHD的人群中观察到PPI降低与压力有关的精神疾病。大量证据支持这一假设。首先，CRF是参与应激反应行为成分的最重要的神经递质之一。其次，CRF的集中输注会降低啮齿动物的PPI。第三，CRF通过位于大脑中调节PPI区域的CRF受体起作用。第四，已知在精神分裂症和PTSD中调节PPI和表达CRF受体的大脑区域异常;尽管CRF的中央输注会降低啮齿动物的PPI，但尚不知道CRF是否通过其对其他神经递质的影响而间接降低PPI。例如血清素，或压力是否通过内源性CRF系统以与外源性CRF调节PPI相同的方式调节PPI。因此，本论文的最终目的是探讨这些主题，并进一步了解CRF和压力影响感觉运动门控的机制。

著录项

  • 作者

    Sutherland, Jane Elizabeth.;

  • 作者单位

    University of Connecticut.;

  • 授予单位 University of Connecticut.;
  • 学科 Neurosciences.;Neurobiology.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 208 p.
  • 总页数 208
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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