Andrew C Harris1, Peter Muelken2, Yayi Swain3, Mary Palumbo4, Vipin Jain5, Maciej L Goniewicz4, Irina Stepanov5, Mark G LeSage6. 1. Department of Medicine, Hennepin Healthcare Research Institute, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA. Electronic address: harr0547@umn.edu. 2. Department of Medicine, Hennepin Healthcare Research Institute, Minneapolis, MN, USA. 3. Department of Medicine, Hennepin Healthcare Research Institute, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA. 4. Department of Health Behavior, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. 5. Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. 6. Department of Medicine, Hennepin Healthcare Research Institute, Minneapolis, MN, USA; Department of Medicine, University of Minnesota, Minneapolis, MN, USA; Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
Abstract
BACKGROUND: Development of preclinical methodology for evaluating the abuse liability of electronic cigarettes (ECs) in adolescents is urgently needed to inform FDA regulation of these products. We previously reported reduced aversive effects of EC liquids containing nicotine and a range of non-nicotine constituents (e.g., propylene glycol, minor tobacco alkaloids) compared to nicotine alone in adult rats as measured using intracranial self-stimulation. The goal of this study was to compare the aversive effects of nicotine alone and EC aerosol extracts in adolescent rats as measured using conditioned taste aversion (CTA), which can be conducted during the brief adolescent period. METHODS AND RESULTS: In Experiment 1, nicotine alone (1.0 or 1.5 mg/kg, s.c.) produced significant CTA in adolescent rats in a two-bottle procedure, thereby establishing a model to study the effects of EC extracts. At a nicotine dose of 1.0 mg/kg, CTA to Vuse Menthol EC extract, but not Aroma E-Juice EC extract, was attenuated compared to nicotine alone during repeated two-bottle CTA tests (Experiment 2a). At a nicotine dose of 0.5 mg/kg, CTA to Vuse Menthol EC extract did not differ from nicotine alone during the first two-bottle CTA test but extinguished more rapidly across repeated two-bottle tests (Experiment 2b). CONCLUSIONS: Non-nicotine constituents in Vuse Menthol EC extracts attenuated CTA in a two-bottle procedure in adolescents. This model may be useful for anticipating the abuse liability of ECs in adolescents and for modeling FDA-mandated changes in product standards for nicotine or other constituents in ECs.
BACKGROUND: Development of preclinical methodology for evaluating the abuse liability of electronic cigarettes (ECs) in adolescents is urgently needed to inform FDA regulation of these products. We previously reported reduced aversive effects of EC liquids containing nicotine and a range of non-nicotine constituents (e.g., propylene glycol, minor tobaccoalkaloids) compared to nicotine alone in adult rats as measured using intracranial self-stimulation. The goal of this study was to compare the aversive effects of nicotine alone and EC aerosol extracts in adolescent rats as measured using conditioned taste aversion (CTA), which can be conducted during the brief adolescent period. METHODS AND RESULTS: In Experiment 1, nicotine alone (1.0 or 1.5 mg/kg, s.c.) produced significant CTA in adolescent rats in a two-bottle procedure, thereby establishing a model to study the effects of EC extracts. At a nicotine dose of 1.0 mg/kg, CTA to Vuse Menthol EC extract, but not Aroma E-Juice EC extract, was attenuated compared to nicotine alone during repeated two-bottle CTA tests (Experiment 2a). At a nicotine dose of 0.5 mg/kg, CTA to Vuse Menthol EC extract did not differ from nicotine alone during the first two-bottle CTA test but extinguished more rapidly across repeated two-bottle tests (Experiment 2b). CONCLUSIONS: Non-nicotine constituents in Vuse Menthol EC extracts attenuated CTA in a two-bottle procedure in adolescents. This model may be useful for anticipating the abuse liability of ECs in adolescents and for modeling FDA-mandated changes in product standards for nicotine or other constituents in ECs.
Authors: Andrew C Harris; Laura Tally; Clare E Schmidt; Peter Muelken; Irina Stepanov; Subhrakanti Saha; Rachel Isaksson Vogel; Mark G LeSage Journal: Drug Alcohol Depend Date: 2014-12-23 Impact factor: 4.492
Authors: Micah L Berman; Warren K Bickel; Andrew C Harris; Mark G LeSage; Richard J O'Connor; Irina Stepanov; Peter G Shields; Dorothy K Hatsukami Journal: Nicotine Tob Res Date: 2018-09-25 Impact factor: 4.244
Authors: Andrew C Harris; Peter Muelken; Zach Haave; Yayi Swain; John R Smethells; Mark G LeSage Journal: Drug Alcohol Depend Date: 2018-10-18 Impact factor: 4.492
Authors: Shakir D Alsharari; Justin R King; Jacob C Nordman; Pretal P Muldoon; Asti Jackson; Andy Z X Zhu; Rachel F Tyndale; Nadine Kabbani; M Imad Damaj Journal: PLoS One Date: 2015-09-10 Impact factor: 3.240
Authors: Cristina Miliano; E Reilly Scott; Laura B Murdaugh; Emma R Gnatowski; Christine L Faunce; Megan S Anderson; Malissa M Reyes; Ann M Gregus; Matthew W Buczynski Journal: J Neurosci Methods Date: 2019-10-12 Impact factor: 2.390
Authors: Andrew C Harris; John R Smethells; Mary Palumbo; Maciej Goniewicz; Mark G LeSage Journal: Int J Environ Res Public Health Date: 2020-01-30 Impact factor: 3.390