NEURAL SUBSTRATES OF PCP'S EFFECT ON SENSORIMOTOR GATING

精神分裂症(SZ)是一种衰弱的神经精神障碍， 表现为各种行为缺陷。当前抗精神病药物 药物，虽然在治疗深圳的许多核心症状上取得了成功， 严重限制了它们的使用，因为深部锥体外系或 粒细胞缺乏性副作用。对神经底物的理解 调解这种疾病的特定缺陷可能会导致揭示 参与SZ的新机制，并可能最终导致 开发新的更安全的治疗方法。预脉冲抑制(PPI)(一种测量 一种感觉运动门控，在这种门控中，温和的前刺激减弱了 对强烈刺激的惊吓反应的大小)是正常的 跨物种的发生是SZ患者所缺乏的。这一损害 在PPI中已经通过给药成功地在大鼠身上建立了模型 非竞争性NMDA拮抗剂，如精神激素苯环利定 (PCP)。本项目的目标是使用这种缺乏的动物模型 PPI以更好地了解PCP的精神分裂效应，并最终 发现SZ患者感觉运动门控受损的新底物。 最初，多个受体介导PPI的假设- 将使用选择性和混合两种方法测试五氯苯酚的破坏性影响 Profile拮抗剂可阻断五氯苯酚的作用。第二个假设 多个大脑区域调节这些影响的测试将使用 颅内药物微量输注技术。总而言之，这个项目寻求 为了确定五氯苯酚的药理和神经解剖学机制- PPI的诱发赤字，以加深我们对 深圳地区感觉运动门控缺陷的神经基础。

Schizophrenia (SZ) is a debilitating neuropsychiatric disorder that is manifested through a variety of behavioral deficits. Current antipsychotic medications, while successful in treating many of the core symptoms of SZ, are seriously limited in their use by profound extrapyramidal or agranulocytotic side effects. An understanding of the neural substrates mediating specific deficits of this disorder may lead to the revelation of novel mechanisms involved in SZ and might ultimately result in the development of new safer treatments. Prepulse inhibition (PPI) (a measure of sensorimotor gating in which a mild prestimulus attenuates the magnitude of the startle response to an intense stimulus) is a normal cross-species occurrence that is deficient in SZ patients. This impairment in PPI has been successfully modelled in rats by administration of noncompetitive NMDA antagonists such as the psychotogen phencyclidine (PCP). The goal of this project is to use this animal model of deficient PPI to better understand the psychotomimetic effects of PCP and ultimately uncover novel substrates of impaired sensorimotor gating in SZ patients. Initially, the hypothesis that multiple receptors mediate the PPI- disruptive effects of PCP will be tested using both selective and mixed profile antagonists to block the effects of PCP. The second hypothesis that multiple brain regions mediate these effects will be tested using intracranial drug microinfusion techniques. In summary, this project seeks to determine the pharmacological and neuroanatomical mechanisms of PCP- induced deficits in PPI in order to further our understanding of the neural substrates of deficient sensorimotor gating in SZ.