NEUROTOXICITY SCREENING

本合同的主要目的是建立方法， 评估滥用药物或可能 对治疗毒瘾有潜在的益处。 化合物被 神经毒性评价将由NIDA提供。 神经毒性 这项工作产生的屏幕将包括敏感的 神经化学和神经解剖学技术， 评价影响单胺能系统和兴奋性毒素的毒性- 诱发神经毒性。 在开发该筛选时，参考化合物 应用于评估技术的灵敏度和可靠性 就业。 啮齿类动物和灵长类动物均将用于这些研究。 初步研究将在啮齿动物中进行，但全面评价试验 化合物将需要灵长类动物研究。 最初的化合物 评价的是伊波替尼;最多可评价两种其他化合物 在本合同期间。对伊博伊博的全面描述 将获得大鼠和灵长类动物的神经毒性，包括二糖- 效应分析、作用部位，以及可能的作用机制。

The major objectives of this contract are to establish methods for evaluating the neurotoxicity of drugs of abuse or medications which may be of potential benefit in treating drug addiction. Compounds to be evaluated for neurotoxicity will be furnished by NIDA. The neurotoxicity screen(s) resulting from this effort will incorporate sensitive neurochemical and neuroanatomical techniques that are capable of evaluating toxicity affecting monoaminergic systems and excitotoxin- induced neurotoxicity. In developing this screen, reference compounds should be used to assess the sensitivity and reliability of the techniques employed. Both rodents and primates will be used in these studies. Initial studies will be conducted in rodents, but full evaluation of test compounds will require primate studies. The initial compound that will be evaluated is ibogaine; up to two additional compounds may be evaluated during the course of this contract. A full characterization of ibogaine's neurotoxicity in both rat and primate will be obtained, including diose- effects analysis, sites of action, and, if possible, mechanism of action.