There is a strong association between heavy alcohol drinking and tobacco use. In laboratory self- administration procedures, both alcohol and nicotine maintain operant responding, and thus are said to function as drug reinforcers. Although human co-use of alcohol and nicotine typically involves self- administration of both, animal studies have focused on the effects of passive administration of one drug on self-administration of the other, limiting study and understanding of behavioral and neurobiological mechanisms underlying co-use. We propose to explicitly examine interactions between nicotine and alcohol in nonhuman primates using a concurrent drug self-administration procedure that will provide long durations of access to both drugs. In addition, we will determine how self-administration changes as a function of increasing work requirements (i.e., number of responses), which is a behavioral economic measure of the strength of the drug as a reinforcer. This analysis will allow exploration of the behavioral mechanisms involved in the co-use of alcohol and nicotine. The proposal has three specific aims: (1) to establish concurrent self-administration of alcohol and nicotine in baboons;(2) to evaluate if concurrently available nicotine and alcohol act as complementary, substitute, or independent reinforcers;and (3) to determine if nicotine replacement reduces the reinforcing efficacy of nicotine and/or alcohol. To address the specific aims, self-administration of alcohol will be established in 5 baboons and rate of self-administration will be determined at different concentrations (2%, 4%, 8% w/v). Next, IV nicotine self-administration will be established and rate of self-administration will be determined at different doses (0.032 - 0.1 mg/kg). After these evaluations, doses will be selected for concurrent access. Alcohol and nicotine will then be concurrently available during 16 hour/day sessions, and rate of self-administration under the baseline conditions will be determined. During the alcohol-only, nicotine- only, and concurrent oral alcohol and IV nicotine self-administration procedures described above, once rate of self-administration has been determined and is stable, reinforcing efficacy as a function of the work requirement will be generated by systematically increasing the response requirement across sessions. During the concurrent access procedure, the response requirement for either alcohol or nicotine will be increased while holding the response requirement for the other drug constant. Finally, non-contingent nicotine will be slowly and continuously infused IV, using a dose similar to that used for nicotine replacement in humans (9.3 mg/day;the equivalent of a 21 mg/day patch in humans). Reinforcing efficacy for both nicotine and alcohol will be determined in the context of the continuously administered nicotine. The data obtained will lead to a better understanding of the mechanisms involved in human co-use of alcohol and nicotine. The procedure will provide a robust, quantifiable method for preclinical evaluation of behavioral and pharmacological treatments for reduction of concurrent alcohol and nicotine use.

Public Health Relevance

There is a strong association between heavy alcohol drinking and tobacco use. Nicotine and alcohol appear to augment use of each other as well as the likelihood of developing dependence on both drugs, which results in major health consequences, including additive risk for some diseases, such as head and neck cancers in individuals who both smoke cigarettes and drink alcoholic beverages. The goal of the proposed studies is to develop a pre-clinical concurrent alcohol and nicotine self-administration procedure that can be used in the present and future studies to answer scientifically and clinically relevant questions about the behavioral mechanisms supporting alcohol and nicotine co-use.

National Institute of Health (NIH)
Exploratory/Developmental Grants (R21)
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Biomedical Research Review Subcommittee (AA)
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Grakalic, Ivana
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Johns Hopkins University
Schools of Medicine
United States
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