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Targeted Tobacco Regulatory Science: Nicotine Dose Effects in Animal Models of Smoking Initiation in Vulnerable Adolescent Subpopulations

Principal Investigator: Mark LeSage

Funding Mechanism: National Institutes of Health – Grant

ID number: 1R01DA042525-01

Award Date: 8/15/2016

Institution: Minneapolis Medical Research Foundation, Inc.


Adolescents with depression and/or Attention Deficit Hyperactivity Disorder (ADHD) have a higher incidence of smoking, start smoking at a younger age, exhibit a faster progression to daily smoking and dependence, and are less successful at quitting than adolescents without depression and/or ADHD. The goal of this study is to determine whether depression and ADHD predispose adolescents to nicotine addiction by lowering their nicotine reinforcement threshold. Experiments involving smoking initiation in adolescents cannot be accomplished in human studies, but can be addressed with animal models. Study aims are to test the hypothesis that the nicotine reinforcement threshold is lower in adolescent rat models of depression (Aim 1) and ADHD (Aim 2) compared to control animals. Researchers will determine the threshold-reinforcing nicotine dose for acquisition of nicotine self-administration, and will assess self-administration persistence during increases in the “price” of nicotine (i.e., difficulty reducing intake), nicotine pharmacokinetics (how quickly the body eliminates nicotine), and sex differences. These data will provide insight into the relative risk of nicotine reinforcement in adolescents, and how the reinforcement threshold is modified by depression and ADHD.

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