Therapy for self-injurious behavior in autism

描述（由申请人提供）：运动症状的一个子集 自闭症的症状包括轻微的刻板到强烈的自我伤害行为。在 过去，这些行为与大脑多巴胺功能障碍有关 但不幸的是，多巴胺拮抗剂的临床试验 效果不佳。公认的啮齿动物自伤行为模型依赖于 新生儿多巴胺损伤，随后对成人给予左旋多巴。这 模型在大鼠中有效，但在小鼠中无效。在一系列的研究中， 杂交以及基因敲除和转基因小鼠，以探索 脑多巴胺能神经元的局部投射的发展， 观察到，新生儿出生后， 对多巴胺能神经元的损害。也就是说，早期多巴胺 损伤激活了脑内胆碱能系统。这一观察结果随后与 诱导成年小鼠的刻板行为和自我伤害行为 用高剂量的安非他明治疗，剂量诱导释放两者 多巴胺和血清素根据这些和其他意见，一个新的 自我伤害行为的动物模型， 脑多巴胺和血清素的作用。此外，基于这一新模式， 利培酮的可能的有益效果，这些拮抗剂 发射机系统，将进行探索。

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.