PHARMACOLOGIC STUDY ON MODELS OF TARDIVE DYSKINESIA

需要一种动物模型来复制一些 迟发性运动障碍所致口腔运动障碍的特点， 过度使用后出现的长寿运动异常 人类使用的抗精神病药。这个模型对研究很有用。 可能涉及迟发性运动障碍的机制，并测试药物 它们有可能阻止甚至逆转马达或生化反应 迟发性运动障碍中出现的异常。测试设备是 可用于测量嘴巴张开的频率，幅度 口部运动、张口率和闭口率。技术 使用图像采集卡记录上下颌骨的相对位置 以1/60秒为增量。在计算机的帮助下，数据被记录下来 嘴张开的幅度与时间的关系。快速傅立叶变换 提供口腔活动的能谱，以便比较 与迟发性运动障碍的低频率口腔运动有关。这个 项目的设计是为了在实验室中建立这个设备来确定 口腔活动异常的大鼠的口腔特征。我们有 研究发现，多巴胺D2拮抗剂诱导的 接受新生6-羟基多巴胺的成年大鼠的口腔活动 大脑中多巴胺能纤维的损伤。类似的增强功能 这些大鼠的口服活动是由DL激动剂产生的。在这个项目中 我们将确定口语活动的特点如何在这些和 相关模型，与显示的迟发性运动障碍模型进行比较。The BMax 纹状体中D1和D2受体的Kd也将被测定 作为每种受体类型的高亲和力形式和低亲和力形式的比率。 生化测定受体复合体的状态将是 为潜在有用的模型制造的。最后一项研究将探讨 调节多巴胺受体的多肽的可能作用，以及 这可能对迟发性运动障碍的治疗有用。一种新的 研究迟发性运动障碍的模型将是巨大的 价值。建议的模型具有额外的好处，因为 口腔活动的诱导似乎是永久性的。

There exists a need for an animal model that would replicate some of the characteristics of the oral dyskinesias that occur in tardive dyskinesia, a long-lived motor abnormality that arises after excessive use of neuroleptic agents in humans. This model would be useful to investigate mechanisms that may be involved in tardive dyskinesia, and to test agents that have a potential to prevent or even reverse the motor or biochemical abnormalities that occur in tardive dyskinesia. Testing equipment is available for measuring the frequency of mouth openings, the amplitude of mouth movement, and the rates of mouth opening and closing. The technology uses frame grabbers to record the relative positions of upper to lower jaws at increments of 1/60 sec. With a computer assist, the data are recorded as amplitude of mouth opening vs. time. Fast fourier transformation provides an energy spectrum of the oral activity, so that comparison can be made with the low frequency mouth movements of tardive dyskinesia. The project is designed to set up this equipment in the laboratory to determine the oral characteristics of rats that have abnormal oral activity. We have found that there is a 10 fold increase in dopamine D2 antagonist-induced oral activity in adult rats that received a neonatal 6-hydroxydopamine lesion of the dopaminergic fibers in the brain. A similar enhancement of oral activity was produced by a Dl agonist in these rats. In this project we shall determine how the features of the oral activity in these and related models, compare with that shown for tardive dyskinesia. The Bmax and Kd for Dl and D2 receptors in the striatum will be determined, as well as the ratio of high and low affinity forms of each receptor type. Biochemical determination of the status of the receptor complex will be made for potentially useful models. The final study will explore the possible effects of a peptide that modulates the dopamine receptor, and which could possibly be useful in treatment of tardive dyskinesia. A new model to investigate aspects of tardive dyskinesia would be of immense value. The proposed model is of added benefit since the susceptibility for induction of oral activity is seemingly permanent.