Preclinical evidence of the effects of sweet flavors: Sweetness increases nicotine intake and seeking.

Abstract

The influence of early exposure to sweet and fruit flavors on subsequent nicotine use behaviors during adolescence remains poorly understood. To address this gap, we utilized a rodent model to simulate childhood flavor exposure and examine its effects on later nicotine use behaviors. We employed a two-bottle choice paradigm in weanling rats to mimic human childhood flavor exposure. Subsequently, we investigated the impact of early exposure to sweet (saccharin) and cherry fruit (benzaldehyde) flavors on adolescent nicotine use behaviors. This included assessing subsequent nicotine acquisition, maintenance, and seeking behaviors using intraoral flavor and intravenous nicotine self-administration. Our findings reveal that rats exposed to saccharin during early development exhibited altered patterns of nicotine intake and seeking behaviors during adolescence. Specifically, rats demonstrated increased nicotine intake and seeking of saccharin flavored solutions when paired with nicotine, indicating a potential predisposition towards nicotine use following childhood flavor exposure. Intraoral benzaldehyde did not affect nicotine reinforcement in early sessions of self-administration, but significantly decreased nicotine reinforcement during later sessions. Both saccharin exposure alone or in combination with benzaldehyde promoted nicotine reinforcement. No significant sex differences in nicotine-related behaviors were observed. This study highlights the significance of early flavor exposure in shaping adolescent nicotine use behaviors. The findings suggest that childhood exposure to sweet flavors may contribute to heightened susceptibility to nicotine use and addiction later in life. Understanding these early influences is crucial for developing targeted interventions to prevent the onset of nicotine addiction during adolescence. Our study highlights the importance of how sweetness can contribute to and possibly even alter the effects of the flavor itself. The sweetness of a tobacco product does not solely stem from sweeteners, but it is also influenced by other components such as the PG/VG ratio (e.g., higher VG) and the inclusion of flavors associated with sweetness (e.g., vanillin and ethyl maltol). Therefore, sweet-associated constituents in tobacco products should be investigated further to inform regulatory policy. We believe that our findings can inform regulatory decisions on controlling sweet associated constituents in tobacco products.