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Assessment of the Addictive Potential of Cotinine, Anatabine, and Myosmine in Rodents

Principal Investigator: Jenny Wiley and Kia Jackson

Funding Mechanism: Research Contract

ID number: HHSF223201310034I

Award Date: 8/5/2014

Institution: Research Triangle Institute

Although nicotine is the primary addictive constituent in tobacco, studies indicate that tobacco also contains non-nicotine constituents (including, but not limited to, anatabine, cotinine, and myosmine) that may have addictive potential.  Previously, researchers used a locomotor activity paradigm to determine behaviorally-active dose ranges of anatabine, cotinine, and myosmine for use in future studies of abuse liability. In this study, the researchers will use that previously-generated data to conduct pharmacological and behavioral studies in adult and adolescent rats to determine the addictive potential of these three constituents and highlight potential differences between adults and adolescents. The rats will be tested using three models of abuse liability -- conditioned place preference, withdrawal signs, and central nervous system activity – that were identified based on acceptable measures of abuse liability used to include constituents on FDA’s harmful and potentially harmful constituent (HPHC) list with an addiction indication. Three doses of each constituent (selected based on the previous research results) will be tested in each paradigm; each does will be tested in 10 rats.  Midbrain dopamine release via in vivo microdialysis will be used to assess effects on central nervous system activity, and nicotine will be used as a positive control in all assessments.  The projected timeframe for completion of these studies is 1.5 years. By identifying tobacco constituents with addictive potential, study results may be used to inform product review or other regulatory activities.

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