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.

自伤行为（SIB）是一个严重的问题， 精神发育迟滞的人。到目前为止， 自我伤害是未知的，确切的治疗方法仍然难以捉摸。在这 我们将使用匹莫林和GBR 12909诱导的大鼠自咬 以建立新纹状体的变化之间的关系 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SIB。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 神经递质释放和行为反应。药理学 操纵将遵循，以建立时间和/或 释放的神经递质的量，对随后的表达 的SIB。这些研究还将确定上述关系是否 发展依赖。同时，拟议的研究将 建立新纹状体在介导匹莫林诱导的 行为。局灶性新纹状体和皮质病变的影响， 新生纹状体对多巴胺（DA）反应的细胞改变 切片将详细探讨。根据初步数据，我们 工作假设是，导致SIB的事件级联 起源于匹莫林诱导的多巴胺释放， 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SIB，但可能不维持SIB 溢出。我们还预测，我们将能够有效地对抗 在这个动物模型中。从这种SIB模型中获得的见解将 显著推进我们对病理生理学和 精神发育迟滞自我伤害的最终药物治疗。