Effects of Sweeteners and Cinnamon Flavor on Oral Nicotine Choice Behaviors

Abstract Introduction Oral nicotine products (ONPs) are emerging as a new nicotine delivery method, with varied types and flavors such as sweeteners and cinnamon. This study evaluates how sucrose, saccharin, and cinnamaldehyde influence nicotine preference, shedding light on the potential appeal of ONPs and how they may impact on harm reduction. Methods For oral choice behavior studies, we utilized a four-bottle choice (BC) test in male and female adult Sprague-Dawley rats. We first examined most common sucrose (1%) and saccharin (0.32%) concentrations as sweet solutions, and quinine (0.01%) as a bitter solution, to determine 4BC sensitivity and ability to distinguish between sweet and bitter tastes. We then performed dose–response analyses with sucrose (0.01%, 0.1%, and 1%), saccharin (0.032%, 0.1%, and 0.32%), and cinnamaldehyde (0.0005%, 0.005%, and 0.05%), in comparison to water in 4BC. Lastly, we tested nicotine (10 µg/mL) choice behaviors in the presence of sweeteners and/or cinnamaldehyde. Results Female and male rats significantly preferred sucrose (1%) and saccharin (0.1% and 0.32%) but not cinnamaldehyde. Moreover, rats differentiated sweet and bitter solutions with the highest preference for saccharin. Sucrose increased nicotine preference in females, but cinnamaldehyde increased nicotine preference in males. Saccharin increased nicotine preference in females, but not in males. Additionally, the combination of cinnamaldehyde and saccharin increased nicotine preference in females. Conclusions We found differential preferences among the test solution concentrations with the highest sweetener concentrations being most preferred. Sweetness value of the nicotine solution played a major role on nicotine preference in females but not in males. Implications Understanding how sweeteners and flavor additives affect oral nicotine choice behavior and nicotine preference in ONPs can guide the development of targeted harm reduction strategies and regulatory policies. By identifying which additives enhance product appeal and potentially influence addiction, this research can inform the creation of safer ONP formulations. This research also supports the utility of evidence-based guidelines for ONP use.