Nicotine Modulation of Ethanol Consumption and Discrimination

描述（由申请人提供）：本指导研究科学家奖（K 01）申请的总体目标是探索乙醇和尼古丁同时给药的行为和药理学后果，同时为候选人（Matthew福特博士）提供丰富的培训环境和多样化的研究经验，以培养其向独立研究者的过渡。候选人将通过与导师/申办者（Kathleen Grant博士）密切合作来补充已经熟悉和建立的自我管理程序，以建立对单一药物和药物混合物的药物辨别能力。除了学习药物辨别程序背后的理论，联想阻断和遮蔽的概念将直接研究乙醇和尼古丁在产生条件药物提示的相互作用。候选人还将熟悉常用的几种药理学策略，以评估区别性药物线索的显着性和特征，例如泛化测试和剂量反应曲线评估。申办者还将指导候选人进行数据分析、数据解释和确定与药物鉴别程序具体相关的程序限制。拟定的研究将测试解决尼古丁暴露史和剂量对乙醇自我给药结果影响的特定目标，并评价尼古丁对拦截乙醇提示所表现出的刺激控制的影响。这种指导培训的机会将允许候选人积累额外的研究技能和经验，在神经药理学和行为的方法来研究酒精和其他滥用药物，并将巩固一个坚实的基础上，站在作为一个独立的主要研究者。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性相互作用。这种研究方法将提供有价值的见解，他们的共同滥用责任的患病率，与额外的潜力，以确定治疗策略的乙醇和尼古丁的共同依赖。

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.