Therapy for self-injurious behavior in autism

描述(由申请人提供)：相关的运动症状的子集 自闭症包括轻微、刻板印象到强烈的自我伤害行为。在……里面 过去，这些行为被认为与大脑多巴胺功能障碍有关 但是，不幸的是，多巴胺拮抗剂的临床试验遇到了 结果很差。公认的自伤行为的啮齿动物模型依赖于 新生儿多巴胺损伤，成年后给予L-多巴。这 该模型在大鼠身上效果良好，但在小鼠身上效果不佳。在一系列研究中使用了原位 杂交以及基因敲除和转基因小鼠的探索 脑多巴胺能神经元地形图投射的研究进展 观察到新生儿后大脑5-羟色胺能系统被激活 对多巴胺能神经元的损伤。也就是说，早期的多巴胺似乎 病变激活了大脑的5-羟色胺能系统。这一观察结果随后被联系起来 对成年小鼠刻板行为和自伤行为的诱导 用高剂量的安非他明治疗，导致两者释放的剂量 多巴胺和5-羟色胺。在这些和其他观察的基础上，一个新的 以双激活为核心的自伤行为动物模型 脑多巴胺和5-羟色胺被提出。另外，基于这个新的模型， 这些药物的拮抗剂利培酮可能的有益作用 发射机系统，将被探索。

DESCRIPTION (provided by applicant): A subset of motoric symptoms associated with autism includes mild, stereotypic to intense, self-injurious behaviors. In the past, these behaviors have been linked to dysfunction of brain dopamine but, unfortunately, clinical trials with dopamine antagonists have met with poor results. The accepted rodent model of self-injurious behavior relies on neonatal dopamine lesions followed by L-dopa administration to the adult. This model works well in rats but not in mice. In a series of studies using in situ hybridization as well as knockout and transgenic mice to explore the development of the topographic projections of brain dopaminergic neurons, it was observed that brain serotinergic systems are activated following neonatal damage to dopaminergic neurons. That is, it appeared that early dopamine lesions activated brain serotinergic systems. This observation was then linked to the induction of stereotypic and self-injurious behaviors in adult mice treated with high doses of amphetamine, doses which induced the release of both dopamine and serotonin. On the basis of these and other observations, a new animal model of self-injurious behaviors centering on the dual activation of brain dopamine and serotonin is proposed. In addition, based on this new model, the possible beneficial effects of risperidone, an antagonist of these transmitter systems, will be explored.