PHARMACOLOGIC STUDY ON MODELS OF TARDIVE DYSKINESIA

需要一种动物模型，其可以复制一些 在迟发性运动障碍中发生的口腔运动障碍的特征， 一种长期的运动异常，在过度使用 精神抑制剂 该模型将有助于研究 可能涉及迟发性运动障碍的机制，并测试试剂 有可能阻止甚至逆转 迟发性运动障碍中出现的异常 检测设备 可用于测量张口频率、 嘴的运动，以及嘴张开和闭合的速率。 技术 使用图像采集卡记录上下颌的相对位置 以1/60秒的增量。 在计算机的帮助下，数据被记录下来 嘴巴张开的幅度与时间的关系。 快速傅立叶变换 提供口腔活动的能量谱，以便比较可以 用迟发性运动障碍的低频嘴部运动来制造。 的 项目旨在建立这种设备在实验室，以确定 具有异常口腔活动的大鼠的口腔特征。 我们有 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服活性 大脑中多巴胺能纤维的损伤。 类似的增强 在这些大鼠中通过D1激动剂产生口服活性。 在这个项目中 我们将确定如何在这些口头活动的特点， 相关模型，与迟发性运动障碍的模型进行比较。 的Bmax 还将测定纹状体中D1和D2受体的Kd 作为每种受体类型的高和低亲和力形式的比率。 受体复合物状态的生化测定将是 为潜在有用的模型而设计。 最后一项研究将探讨 调节多巴胺受体的肽的可能作用，以及 其可能用于治疗迟发性运动障碍。 一个新 研究迟发性运动障碍的模型将是巨大的 值 所提出的模型是额外的好处，因为敏感性 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.