Koenig James I, Elmer Gregory I, Shepard Paul D, Lee Paul R, Mayo Cheryl, Joy Brian, Hercher Ericka, Brady Dana L
Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, P.O. Box 21247, Baltimore, MD 21228, USA.
Behav Brain Res. 2005 Jan 30;156(2):251-61. doi: 10.1016/j.bbr.2004.05.030.
Exposure to stress during gestation induces marked changes in the behavior of the affected offspring. Examining the consequences of prenatal stress may prove useful in understanding more about the origins of schizophrenia because a number of clinical investigations have suggested that developmental insults are associated with an increased incidence of schizophrenia. The purpose of these studies is to investigate the effects of stress during gestation on the behaviors of the adult male rat offspring with an emphasis on developing a heuristic animal model of schizophrenia. Pregnant female Sprague-Dawley rats were exposed to a novel variable stress paradigm during either the second or third week of gestation. Behavioral and neuroendocrinological consequences of prenatal stress exposure were evaluated in the male offspring on postnatal day 35 or 56. Prenatal stress exposure during the third week of pregnancy caused adult male rats to exhibit prolonged elevation in plasma glucocorticoid levels following acute exposure to restraint stress indicative of diminished glucocorticoid negative feedback. Similarly, exposure to stress during the third week of pregnancy elicited an enhanced locomotor response to the psychomotor stimulant amphetamine on postnatal day 56 but not on postnatal day 35. In addition, prepulse inhibition of the acoustic startle response was diminished across a range of prepulse stimulus intensities in prenatally stressed adult male rats. Similarly, prenatally stressed rats showed evidence of a disruption in auditory sensory gating as measured by the N40 response. Taken together, these findings suggest that prenatal stress exposure significantly changed many facets of adult rat behavior. Interestingly, the behaviors that are altered have been used to validate animal models of schizophrenia and therefore, suggest that this preparation may be useful to learn more about some aspects of the pathophysiology of schizophrenia.
孕期暴露于应激会导致受影响后代的行为发生显著变化。研究产前应激的后果可能有助于更深入地了解精神分裂症的起源,因为多项临床研究表明,发育损伤与精神分裂症发病率的增加有关。这些研究的目的是调查孕期应激对成年雄性大鼠后代行为的影响,重点是建立一种启发式的精神分裂症动物模型。将怀孕的雌性斯普拉格-道利大鼠在孕期的第二周或第三周暴露于一种新的可变应激范式。在出生后第35天或56天对雄性后代进行产前应激暴露的行为和神经内分泌后果评估。孕期第三周的产前应激暴露导致成年雄性大鼠在急性暴露于束缚应激后血浆糖皮质激素水平长时间升高,这表明糖皮质激素负反馈减弱。同样,孕期第三周的应激暴露在出生后第56天而非第35天引起对精神运动兴奋剂苯丙胺的运动反应增强。此外,在一系列预脉冲刺激强度下,产前应激成年雄性大鼠的听觉惊跳反应的预脉冲抑制减弱。同样,产前应激大鼠表现出听觉感觉门控中断的证据,这通过N40反应来测量。综上所述,这些发现表明产前应激暴露显著改变了成年大鼠行为的许多方面。有趣的是,被改变的行为已被用于验证精神分裂症的动物模型,因此,表明这种实验准备可能有助于更多地了解精神分裂症病理生理学的某些方面。