Chronic oral nicotine exposure decreases aversive taste of nicotine, increases nicotine withdrawal and reinstatement, but cherry flavor does not alter nicotine?s effects in adolescent rats

Although e-cigarette use among youth is recognized as an epidemic, there is limited understanding regarding nicotine's orosensory and chronic use effects in youth, and how fruit e-cigarette flavorings may influence nic-otine's effects. We aimed to characterize the orosensory and chronic use effects of nicotine in adolescent rats. We also determined the acute and chronic effects of benzaldehyde, a cherry/berry/almond flavoring, on nicotine's taste, consumption, withdrawal, and reinstatement. Rats were examined for their acute taste responses to the different nicotine concentrations. The effects of chronic exposure on nicotine's taste, withdrawal, and rein-statement were also determined. In addition, impact of benzaldehyde on these nicotine use behaviors was evaluated.While taste responses to low nicotine concentrations did not differ from water, high nicotine concentrations induced aversion. Aversive responses to nicotine that were observed in naive animals vanished after chronic nicotine exposure, indicating the development of tolerance to nicotine's aversive taste. Additionally, nicotine abstinence after chronic exposure induced withdrawal. Following abstinence, animals reinstated nicotine use. Further, animals showed higher preference to nicotine after reinstatement, compared to preference values before nicotine withdrawal. Benzaldehyde did not alter nicotine's taste reactivity, withdrawal, and reinstatement ex-periments. Some sex differences were found in benzaldehyde's taste response and choice behavior experiments.