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Animal Models to Inform FDA Tobacco Regulation: Assessing the Relative Abuse Liability of Different Classes of Tobacco Products

Animal Models to Inform FDA Tobacco Regulation: Assessing the Relative Abuse Liability of Different Classes of Tobacco Products

Principal Investigator(s): Andrew Charles Harris and Mark G. LeSage

Funding Mechanism: NIH Grant

ID number: 1R01DA046318-01A1

Award Date: 8/27/2018

Institution: Minneapolis Medical Research Foundation, Inc.


Although nicotine is the main addictive chemical in tobacco, other chemicals may also contribute to tobacco addiction. The goal is to understand whether non-nicotine constituents unique to cigarette smoke contribute to differences in abuse liability between conventional combusted cigarettes and non-combusted products like e-cigarettes, smokeless tobacco, and nicotine replacement therapy (NRT), using rat models of abuse liability including self-administration. Researchers will measure levels of non-nicotine constituents (e.g., monoamine oxidase [MAO] inhibitors, volatile organic compounds [VOCs]) and identify the specific constituents that may be responsible for observed differences in abuse liability.  Study aims are: (1) to compare demand for cigarette smoke extract to nicotine dose-equivalent concentrations of smokeless tobacco extract, e-cigarette extract, and nicotine alone when each is available in isolation or under choice procedures to determine relative reinforcing efficacy and substitutability of the extracts and nicotine alone; (2) to compare reinforcement-enhancing and aversive effects between extracts and nicotine alone; and (3) to evaluate the reinforcement-enhancing and aversive effects of isolated MAO inhibitors and VOCs when administered alone or in combination with nicotine. Findings will provide information about how chemicals other than nicotine contribute to tobacco addiction and may inform regulatory activities.