Social Stress and Sensorimotor Gating Deficits in Rats

描述（由申请人提供）：环境压力因素被认为会触发易受伤害个体的精神分裂症发作或复发。症状包括感觉泛洪和认知碎片，这是感觉运动门控缺陷的结果。感觉运动门控可以通过定量测试来测量，该测试评估在出现较弱的预脉冲刺激后，对声脉冲刺激的惊吓反应的减少。这种脉冲前抑制声惊反应（PPI）在精神分裂症患者和伏隔核和/或边缘前和边缘下前额皮质多巴胺能异常的大鼠中被破坏。同种动物之间紧张的社会互动会导致多巴胺功能障碍，并扰乱PPI。

DESCRIPTION (provided by applicant): Environmental stressors are thought to trigger the onset or relapse of schizophrenia in vulnerable individuals. Symptoms include sensory flooding and cognitive fragmentation, which are the result of sensorimotor gating deficits. Sensorimotor gating can be measured using a quantitative test that assesses reduction of the startle response to an acoustic pulse stimulus after presentation of a weaker prepulse stimulus. Such prepulse inhibition of the acoustic startle response (PPI) is disrupted in patients with schizophrenia and in rats with dopaminergic abnormalities in the nucleus accumbens and/or prelimbic and infralimbic prefrontal cortex. A stressful social interaction between conspecific animals causes such dopamine dysfunction, and disrupts PPI. The long-range goal of this project is to determine the cellular and molecular mechanisms by which social stress can produce symptoms of schizophrenia. An animal model of sensorimotor gating will be used to examine the neurobiological responses leading to PPI disruption after repeated social stress exposure, initially focusing on the role of prelimbic/infralimbic cortex. The specific aims of the project are (1) to determine the time course of PPI disruption induced by repeated social stress exposure, elucidating the involvement of D2-like receptors in the nucleus accumbens, (2) to ascertain whether tonic dopamine activity in prelimbic/infralimbic cortex is related to social stress-induced PPI disruption, (3) to quantify and characterize the persistent expression of Fos-related antigen(s) in prelimbic/infralimbic cortex following repeated social stress, (4) to characterize the neuroanatomical connections of cortical neurons expressing Fos-related antigens after repeated social stress exposure, and (5) to determine whether social stress-induced elevation of corticosterone level leads to PPI disruption by inhibiting corticosterone synthesis during stress exposure. Together, these studies will produce novel data on the cellular and molecular effects of a salient social stressor, which causes long-lasting sensorimotor gating deficits in rodents, and may trigger the onset or relapse of schizophrenia in patients.