Nicotine Modulation of Ethanol Consumption and Discrimination

描述(由申请者提供)：这个指导研究科学家奖(K01)申请的总体目标是探索同时给予乙醇和尼古丁的行为和药理学后果，同时为候选人(马修·福特博士)提供丰富的培训环境和多样化的研究经验，这将有助于他向独立研究人员的转变。候选人将通过与导师/赞助人(凯瑟琳·格兰特博士)密切合作，建立培训单一药物和药物混合物的药物鉴别力的熟练程度，来补充已经熟悉和建立的自我管理程序。除了学习药物辨别程序背后的理论外，还将直接研究与酒精和尼古丁相互作用有关的联想阻断和遮蔽的概念，以产生条件药物线索。应聘者还将熟悉几种常用的药理学策略，如泛化测试和剂量-反应曲线评估，这些策略通常用于评估辨别性药物线索的显著程度和特征。赞助商还将指导候选人进行数据分析、数据解释和查明与药物歧视程序具体相关的程序限制。拟议的研究将测试特定的目标，以解决尼古丁暴露历史和剂量对乙醇自身给药结果的影响，并评估尼古丁对截取乙醇线索所显示的刺激控制的影响。这一有指导的培训机会将使应聘者在研究酒精和其他滥用药物的神经药理学和行为方法方面积累更多的研究技能和经验，并将巩固作为独立首席研究员的坚实基础。相关性：据估计，90%的酗酒者有吸烟行为。通过对尼古丁和乙醇同时给药的研究，本研究旨在更全面地了解尼古丁和乙醇之间的功能相互作用。这种调查方法将为他们共同滥用责任的普遍性提供有价值的见解，并有可能确定乙醇和尼古丁共同依赖的治疗策略。

DESCRIPTION (provided by applicant): The overall goal of this Mentored Research Scientist Award (K01) application is to explore the behavioral and pharmacological ramifications of concurrent ethanol and nicotine administration while providing the candidate (Dr. Matthew Ford) with an enriched training environment and a diversified research experience that will serve to nurture his transition to an independent investigator. The candidate will complement already familiar and established self-administration procedures by working closely with the mentor/sponsor (Dr. Kathleen Grant) to establish proficiency in training drug discriminations for single drugs and drug mixtures. In addition to learning the theory behind the drug discrimination procedure, the concepts of associative blocking and overshadowing will be directly studied in relation to ethanol and nicotine interactions in the generation of a conditioned drug cue. The candidate will also become familiar with several pharmacological strategies that are commonly employed to evaluate the salience and characteristics of a discriminative drug cue, such as, generalization testing and dose-response curve assessments. The sponsor will also guide the candidate in the practice of data analysis, data interpretation and the identification of procedural limitations as specifically related to the drug discrimination procedure. The proposed studies will test specific aims that address the influence of nicotine exposure history and dose on ethanol selfadministration outcomes and evaluate the impact of nicotine on the stimulus control exhibited by an interceptive ethanol cue. This mentored training opportunity will permit the candidate to accumulate additional research skills and experience in neuropharmacological and behavioral approaches to studying alcohol and other abused drugs, and will cement a solid foundation on which to stand as an independent principal investigator. Relevance: An estimated 90% of alcoholics engage in smoking behavior. Through the investigation of concurrent nicotine and ethanol administration, this research application seeks to arrive at a more complete understanding of the functional interactions between nicotine and ethanol. This investigational approach will provide valuable insights into the prevalence of their co-abuse liability, with the added potential to identify treatment strategies for ethanol and nicotine co-dependence.