Social Stress and Sensorimotor Gating Deficits in Rats

点击翻译按钮获取中文摘要

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.