Development Of A Mouse Model To Study E-Cigarettes And The Role Of A Fruit Flavorant On Adolescent Nicotine Reward

Adolescents are using electronic nicotine devices (i.e. ‘vaping’) at high rates, due in part to the availability of appealing flavors (e.g. ‘fruit’ and ‘candy’). Observational data suggests that these flavors may increase nicotine consumption in adolescents, but the underlying mechanisms remain unclear. This thesis set out to better understand whether and how a fruit flavor additive (e.g. strawberry) might affect adolescent nicotine use, with the main hypothesis that flavor additives would increase nicotine reward and consumption through mesolimbic DA mechanisms. Evidence of a fruit flavor’s ability to increase nicotine consumption was apparent through two modes of nicotine consumption: oral nicotine self-administration and e-cigarette vapor inhalation. Female adolescent mice consumed higher doses of nicotine if they had access to a fruit-flavored nicotine solution, an effect not observed in adolescent male mice. However, both male and female mice had higher plasma cotinine concentrations (a proxy for nicotine exposure) after being vaped with a strawberry flavored nicotine vapor compared to mice vaped with an unflavored nicotine vapor. This increase in plasma cotinine concentrations was associated with increased ‘sniffing’ in response to flavored nicotine vapors. Despite increased nicotine consumption, there was no evidence to support the hypothesis that the strawberry flavor additive increased nicotine reward or increased mesolimbic DA activity. Neither nicotine vapor CPP, nor the concentration of DA in the NAc were enhanced by the addition of a strawberry flavor additive. Instead, the additive may promote nicotine consumption by increasing its palatability, which would implicate other neurotransmitter systems (e.g. opioid and endocannabinoids). In support of this hypothesis, high intensity sniffing occurs in mice in response to attractive odors. Still, more work is necessary to strengthen this hypothesis. Furthermore, this data does not rule out the possibility that mesolimbic DA will affect nicotine use in e-cigarettes, as many e-cigarette sweeteners and additives remain untested. However, it suggests that future research in this field should not neglect the possibility that non-DAergic mechanisms, including hedonic and sensory, could have meaningful impacts on nicotine consumption, which is of particular concern during adolescence while the brain is still developing