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  1. Tobacco Science & Research

Nicotine Self-Administration with Flavor Cues

Principal Investigator: Matthew Palmatier

Funding Mechanism: National Institutes of Health - Grant

ID number: 1 R15 DA038843-01A1

Award Date: 8/20/2015

Institution: East Tennessee State University

Flavor additives in tobacco products and e-cigarettes may increase their appeal and encourage experimentation, repeated use, and dependence, even when only small amounts of nicotine are available. Many of the flavors in tobacco products are “incentives” - stimuli that have become rewards because of their inclusion in foods and beverages. For example, strawberry and licorice flavors become incentives because they are consumed in sweet foods that are high in calories before people use tobacco or vapor products. The goal of this study is to evaluate whether the psychological value of flavor additives interacts with nicotine to increase motivation to self-administer the drug in a rat model. Specific aims are: (1) to investigate which specific flavors (menthol, licorice, strawberry, or cocoa) promote the most nicotine self-administration; (2) to investigate whether these flavor incentives increase dependence-like behavior when they are self-administered with nicotine; and (3) to investigate whether the combination of incentive flavors and nicotine will increase the release of dopamine, a brain chemical that contributes to compulsive substance use and dependence. Researchers will give one flavor (e.g., menthol) psychological appeal by pairing it with sugar (e.g., incentive flavor); a second “unsweetened” flavor will serve as a control (e.g., neutral flavor). During testing, rats will be tethered to a leash that can deliver nicotine intravenously. One of four nicotine doses (0, 3, 10, or 60 ug/kg/infusion) will be delivered when rats lick a sipper tube with the flavors. Each time the rat receives a nicotine infusion, a few drips of a flavor (incentive or neutral) will be released into the sipper tube. This procedure mimics the fast delivery of nicotine to the brain in conjunction with the oral perception of flavor additives during vaping and smoking. To more closely model smoking and vaping, the flavors will be presented “unsweetened” during these tests. Based on past research and preliminary data, the investigators have hypothesized that an interaction between nicotine and the incentive flavors will promote drug-taking at low doses, increase the motivation for nicotine, increase levels of dopamine in the brain, and increase dependence-like behavior. Findings may inform regulatory activities related to flavors.