PHARMACOLOGY AND TOXICOLOGY OF METHAMPHETAMINE ABUSE

描述：（申请人摘要） 这是Glen R博士的高级科学家奖提案。汉森 博士 汉森是药理学系的终身教授， 犹他州大学的毒理学。 他一直在积极吸毒 研究超过15年，并作出了重要贡献， 阐明：（a）多巴胺系统在由以下引起的神经毒性中的作用： 安非他明类似物;（B）活性氧类在介导 安非他明类似物引起的单胺能变化;（c） 滥用兴奋剂对神经肽系统的影响;（d）多巴胺的作用 受体亚型在调节肾上腺素和边缘系统 神经肽系统 汉森博士目前将40-50%的时间用于 研究和学生辅导，而他的努力的50-60%是占用 教学，部门和学院的责任。 这位资深科学家 该奖项将使汉森博士增加他的研究工作，约 百分之八十 在获得该奖项的支持期间， 它测试了以下主要假设：（a）生成 多巴胺相关的活性氧是一个主要的贡献者， 神经化学缺陷发生在纹状体单胺能系统后， 高剂量甲基安非他明（METH）;（B）甲卡西酮，一种较新的 设计师安非他明，施加深刻的短期和长期影响， 锥体外系和边缘单胺能系统，并具有显著的 神经毒性潜力;（c）甲基急性和选择性地改变性质， 多巴胺转运蛋白以可逆方式的功能;（d）低， 高剂量METH优先影响间接（纹状体-苍白球） 和直接（纹状体-黑质）传出通路到基底神经节输出 （e）人类神经肽系统发生变化 暴露于滥用的强效兴奋剂，就像在老鼠身上观察到的那样， 在使用相同的药物治疗后。 研究时间的增加 高级科学家奖将使汉森博士能够开发 他的实验室需要新技术的专业知识来测试这些 假设，如：（a）自由基分析;（B）转运蛋白功能 和配体测定;（c）神经肽前体的原位杂交 mRNA。 该奖项将帮助汉森博士更有效地指导 缺乏经验的研究人员在本科生，研究生，博士后和 随着这些发展中的科学家的成熟和建立， 一般来说，他们自己从事神经科学研究， 特别的。 此外，作为导师，汉森博士将特别 支持代表人数不足的少数群体参与药物滥用 research.

DESCRIPTION: (Applicant's Abstract) This is a Senior Scientist Award proposal for Dr. Glen R. Hanson. Dr. Hanson is a tenured professor in the Department of Pharmacology and Toxicology at the University of Utah. He has been active in drug abuse research for over 15 years and has made important contributions to elucidating: (a) the role of dopamine systems in neurotoxicity caused by amphetamine analogs; (b) the role of reactive oxygen species in mediating monoaminergic changes caused by amphetamine analogs; (c) the influence of the stimulants of abuse on neuropeptide systems; (d) the role of dopamine receptor subtypes in the regulation of extrapyrarnidal and limbic neuropeptide systems. Dr. Hanson currently devotes 40-50% of his time to research and student mentoring while 50-60% of his effort is occupied by teaching, departmental and college responsibilities. This Senior Scientist Award will allow Dr. Hanson to increase his research effort to approximately 80%. During the time of support by this award, he will direct research which tests the following principal hypotheses: (a) the generation of dopamine-related reactive oxygen species is a major contributor to the neurochemical deficits occurring in the striatal monoaminergic systems after high doses of methamphetamine (METH); (b) methcathinone, a relatively new designer amphetamine, exerts profound short-and long-term effects on extrapyramidal and limbic monoaminergic systems and has significant neurotoxic potential; (c) METH acutely and selectively alters the nature and function of the dopamine transporter in a reversible manner; (d) low and high doses of METH preferentially influence the indirect (striatal-pallidal) and direct (striatal-nigral) efferent pathways to the basal ganglia output nuclei, respectively; (e) changes in neuropeptide systems occur in humans exposed to the potent stimulants of abuse much like that observed in rats after treatment with these same drugs. The increase in research time resulting from a Senior Scientist Award will allow Dr. Hanson to develop expertise in technologies new to his laboratory required to test these hypotheses, such as: (a) free radical analysis; (b) transporter function and ligand assays; (c) in situ hybridization for neuropeptide precursor mRNA. This award will help Dr. Hanson to mentor more effectively inexperienced researchers at the undergraduate, graduate, postdoctoral and young faculty levels as these developing scientists mature and establish themselves in neuroscience research in general, and drug abuse research in particular. In addition, as a mentor Dr. Hanson will be especially supportive of the involvement of underrepresented minorities in drug abuse research.