Behavioral Pharmacology of Drug Self-Administration

描述（由申请人提供）：这是NIDA高级科学家奖（K05）的新申请。 候选人是威廉·L。伍尔弗顿博士，密西西比大学医学中心精神病学和药理学教授。 他有30年的药物滥用研究历史，在过去的18年里一直受到NIDA的资助。 他的主要研究领域是非人类灵长类动物的静脉注射药物自我管理。 这种动物模型在我们对吸毒的理解的演变中发挥了核心作用。 PI建议使用新的方法来扩展这个模型，以详细研究控制药物服用的神经生物学和行为机制。 拟议的研究反映了NIDA目前的赠款支持。 神经生物学的目标集中在药效学和药代动力学机制的作用，决定了单胺转运体作用的药物的增强作用。 此外，我们将研究的可能性，这些化合物的自我管理是部分由涉及单胺转运蛋白或其他神经递质系统的厌恶效应。 行为目标围绕着这样一个假设，即控制选择的正常机制的丧失会导致药物自我给药失去控制，这是药物滥用的一个明确特征。 药物选择将在选择的主要理论模型的背景下进行研究，包括匹配，延迟折扣和行为经济学。 总的来说，这项研究将扩展和完善我们的神经生物学和吸毒行为决定因素的知识。 此外，它将对治疗药物的开发产生重要影响，并建议行为方法来修改自我给药的选择。 这个K05将确保候选人可以集中精力在他的职业生涯作为一个药物滥用科学家。 持续的职业发展将来自新的研究项目和以前项目的新问题的结合，以及新的和持续的合作。 这将由UMC庞大而活跃的神经科学社区促进。 在这两个前和博士后水平的学员将参加这项研究计划。 一个重要的目标将是为他们提供所需的职业生涯的研究药物自我管理的神经行为药理学的技能。 此外，候选人将继续参与其他有助于整体职业发展的专业活动，例如教学和期刊编辑委员会，政府咨询委员会和科学组织的积极成员。

DESCRIPTION (provided by applicant): This is a new application for a NIDA Senior Scientist Award (K05). The candidate is William L. Woolverton, Ph.D., Professor of Psychiatry and Pharmacology at the University of Mississippi Medical Center (UMC). He has a 30-year history of drug abuse research and has been funded continuously by NIDA for the past 18 years. His primary area of research is intravenous drug self-administration by non-human primates. This animal model has played a central role in the evolution of our understanding of drug taking. The PI proposes to extend this model using novel approaches to examine in detail neurobiological and behavioral mechanisms that control drug taking. The proposed research reflects current grant support from NIDA. Neurobiological aims focus on the role of pharmacodynamic and pharmacokinetic mechanisms that determine the reinforcing effects of drugs that act at monoamine transporters. In addition, we will examine the possibility that self-administration of these compounds is partially determined by aversive effects that involve monoamine transporters or other neurotransmitter systems. Behavioral aims revolve around the hypothesis that loss of normal mechanisms controlling choice contributes to loss of control of drug self-administration, a defining feature of drug abuse. Drug choice will be examined in the context of major theoretical models of choice, including matching, delay discounting, and behavioral economics. Overall, this research will extend and refine our knowledge of neurobiological and behavioral determinants of drug taking. In addition, it will have important implications for the development of treatment medications, and suggest behavioral approaches to modifying the choice to self-administer a drug. This K05 will ensure that the candidate can concentrate his effort on his career as a drug abuse scientist. Continued career development will come from a combination of new research projects and new questions from previous projects, as well as to new and continuing collaborations. This will be facilitated by the large and active neuroscience community at UMC. Trainees at both pre- and postdoctoral levels will participate in this research program. An important goal will be to provide them with the skills needed for a career of research on the neurobehavioral pharmacology of drug self-administration. In addition, the candidate will continue to participate in other professional activities that contribute to overall career development, such as teaching and active membership on journal editorial boards, government advisory committees, and scientific organizations.