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. ? ? ?
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