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William L. Woolverton博士，他是密西西比大学医学中心（UMC）的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年里一直得到NIDA的资助。他的主要研究领域是非人类灵长类动物的静脉给药。这种动物模型在我们理解药物服用的过程中发挥了核心作用。PI建议使用新的方法来扩展这个模型，以详细检查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目前的拨款支持。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，这些机制决定了药物对单胺转运体的强化作用。此外，我们将研究这些化合物的自我给药的可能性部分取决于涉及单胺转运体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，即失去控制选择的正常机制会导致失去对药物自我给药的控制，这是药物滥用的一个决定性特征。药物选择将在选择的主要理论模型的背景下进行检查，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对药物服用的神经生物学和行为决定因素的认识。此外，它将对治疗药物的发展产生重要影响，并提出改变自我用药选择的行为方法。

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.