SELF INJURIOUS BEHAVIOR IN MENTAL RETARDATION

智力低下的自残行为

• 批准号: 2673934
• 负责人: Bryan H King
• 金额: $ 0.42万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 1998-09-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2673934
• 关键词: animal developmental psychology; behavioral /social science research tag; cholecystokinin; corpus striatum; disease /disorder model; dizocilpine; dopamine antagonists; dopamine receptor; electrophysiology; endogenous opioid; glutamate receptor; glutamates; high performance liquid chromatography; injury; laboratory rat; mental retardation; microdialysis; naltrexone; neurons; neuropharmacology; neurotransmitter metabolism; oxazolidone; psychopharmacology; radioimmunoassay; serotonin

Self-injurious behavior (SIB) is a significant problem for many individuals with mental retardation. As yet, the mechanisms that underlie self-injury are unknown, and definitive treatments remain elusive. In this project we will use pemoline and GBR12909-induced self-biting in the rat to establish the relationship between changes in neostriatal neurotransmitter release and self-biting behavior, and also to determine the critical role of the neostriatum for the initiation and/or maintenance of SIB. The first aim is approached by dose-response studies which determine the relationship between neostriatal pemoline levels, patterns of neurotransmitter release, and behavioral responses. Pharmacologic manipulations will follow, to establish the primacy of the timing and/or the quantity of neurotransmitter(s) released, on the subsequent expression of SIB. These studies will also determine if the above relationships are developmentally-dependant. In concurrent aims, the proposed studies will establish the specificity of the neostriatum in mediating pemoline-induced behaviors. The effects of focal neostriatal and cortical lesions, and cellular alterations in the response to dopamine (DA) in neostriatal slices will be explored in detail. Based upon preliminary data, our working hypothesis is that the cascade of events which leads to SIB originates with pemoline-induced dopamine release, initially sensitizing neostriatal neurons through glutamate dependant mechanisms, and later initiating though perhaps not maintaining SIB through neostriatal DA overflow. We also predict that we will be able to effectively antagonize SIB in this animal model. Insights from this model of SIB will significantly advance our understanding of both the pathophysiology and ultimate pharmacotherapy of self-injury in mental retardation.

自残行为（SIB）对许多人来说是一个严重的问题 智力低下的人。迄今为止，其背后的机制 自伤的情况尚不清楚，并且尚无明确的治疗方法。在这个 项目中我们将使用匹莫林和 GBR12909 诱导大鼠自咬 建立新纹状体变化之间的关系 神经递质释放和自咬行为，并确定 新纹状体对于启动和/或维持的关键作用 SIB 的。第一个目标是通过剂量反应研究来实现的， 确定新纹状体匹莫林水平、模式之间的关系 神经递质释放和行为反应。药理作用 随后将进行操纵，以确定时间和/或的首要地位 随后表达时释放的神经递质的数量 SIB 的。这些研究还将确定上述关系是否成立 发展依赖。在同时的目标中，拟议的研究将 建立新纹状体在介导匹莫林诱导的特异性 行为。局灶性新纹状体和皮质病变的影响，以及 新纹状体对多巴胺（DA）反应的细胞改变 将详细探讨切片。根据初步数据，我们 工作假设是导致 SIB 的级联事件 起源于匹莫林诱导的多巴胺释放，最初致敏 新纹状体神经元通过谷氨酸依赖机制，后来 通过新纹状体 DA 启动但可能不维持 SIB 溢出。我们还预测我们将能够有效地对抗 该动物模型中的 SIB。从这个 SIB 模型中获得的见解将 显着增进了我们对病理生理学和 精神发育迟滞自伤的终极药物疗法。