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Non-nicotine constituents in e-cigarette aerosol extract attenuate nicotine's aversive effects in adolescent rats.

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.

SUBMITTER: Harris AC

PROVIDER: S-EPMC6941564 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Non-nicotine constituents in e-cigarette aerosol extract attenuate nicotine's aversive effects in adolescent rats.

Harris Andrew C AC Muelken Peter P Swain Yayi Y Palumbo Mary M Jain Vipin V Goniewicz Maciej L ML Stepanov Irina I LeSage Mark G MG

Drug and alcohol dependence 20190801

<h4>Background</h4>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 compa ...[more]

PMID: 31404849

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Project description:Electronic cigarettes (ECs) and tobacco cigarettes (TCs) both release nicotine, a sympathomimetic drug. We hypothesized that baseline heart rate variability (HRV) and hemodynamics would be similar in chronic EC and TC smokers and that after acute EC use, changes in HRV and hemodynamics would be attributable to nicotine, not non-nicotine, constituents in EC aerosol. In 100 smokers, including 58 chronic EC users and 42 TC smokers, baseline HRV and hemodynamics [blood pressure (BP) and heart rate (HR)] were compared. To isolate the acute effects of nicotine vs. non-nicotine constituents in EC aerosol, we compared changes in HRV, BP, and HR in EC users after using an EC with nicotine (ECN), EC without nicotine (EC0), nicotine inhaler (NI), or sham vaping (control). Outcomes were also compared with TC smokers after smoking one TC. Baseline HRV and hemodynamics were not different in chronic EC users and TC smokers. In EC users, BP and HR, but not HRV outcomes, increased only after using the ECN, consistent with a nicotine effect on BP and HR. Similarly, in TC smokers, BP and HR but not HRV outcomes increased after smoking one TC. Despite a similar increase in nicotine, the hemodynamic increases were significantly greater after TC smokers smoked one TC compared with the increases after EC users used the ECN. In conclusion, chronic EC and TC smokers exhibit a similar pattern of baseline HRV. Acute increases in BP and HR in EC users are attributable to nicotine, not non-nicotine, constituents in EC aerosol. The greater acute pressor effects after TC compared with ECN may be attributable to non-nicotine, combusted constituents in TC smoke.NEW & NOTEWORTHY Chronic electronic cigarette (EC) users and tobacco cigarette (TC) smokers exhibit a similar level of sympathetic nerve activity as estimated by heart rate variability. Acute increases in blood pressure (BP) and heart rate in EC users are attribute to nicotine, not non-nicotine, constituents in EC aerosol. Acute TC smoking increased BP significantly more than acute EC use, despite similar increases in plasma nicotine, suggestive of additional adverse vascular effects attributable to combusted, non-nicotine constituents in TC smoke.

Project description:IntroductionTo examine the interaction between an added flavoring (cherry) and nicotine on the perception of electronic cigarette (e-cigarette) aerosol and how this impacts the appeal of flavored liquids for e-cigarette (e-liquids).MethodsA total of 19 subjects (13 male, 6 female) vaped six commercially available e-liquids with varying contents of nicotine (0, 6, 12 mg/mL) and cherry flavor (4.7% or 9.3% vol/vol). For each e-liquid, subjects first rated overall liking/disliking of the aerosol using the Labeled Hedonic Scale, followed by perceived intensities of sweetness, bitterness, harshness (irritation), and cherry flavor of the aerosol using the general version of Labeled Magnitude Scale.ResultsThe main findings were that (1) added nicotine increased perceived irritation and bitterness, and decreased the perceived sweetness of the e-cigarette aerosol; (2) cherry flavoring added a characteristic "cherry flavor" and an increase in the flavoring concentration from 4.7% to 9.3% tended to increase perceived intensities of sweetness, harshness, and bitterness; and (3) hedonic ratings of the e-cigarette aerosol decreased as nicotine level increased, but were not affected by flavor level.ConclusionsOur findings indicate that the appeal of the e-cigarette aerosol decreases as nicotine concentration increases. Conversely, perceived sweetness improved liking. An increase in the concentration of cherry flavoring did not appear to impact any of the measured attributes to a significant degree.ImplicationsThis work demonstrates that the perception of specific sensory attributes of e-cigarettes and their overall appeal are affected by the e-liquid constituents. Most significantly, the results suggest that nicotine decreases the sensory appeal of e-cigarettes by contributing to the perceived irritation and bitterness of the aerosol. These data have implications for the role that nicotine plays in the sensory perception and appeal of e-cigarettes aerosol and further how these sensory factors can be modulated by sweet flavoring.

Project description:IntroductionAlthough nearly 90% of current smokers initiated tobacco use during adolescence, little is known about reinforcement by nicotine in adolescents. Researchers are currently investigating whether a potential public health policy setting a tobacco product standard with very low nicotine levels would improve public health, and it is essential to understand whether data generated in adults translates to adolescents, particularly as it relates to the threshold dose of nicotine required to support smoking. The present study compared self-administration of low doses of nicotine between adolescent and adult rats.MethodsAdolescent (postnatal day [P] 30) and adult (P90) male and female rats were allowed to nosepoke to receive intravenous infusions of nicotine (3-100 μg/kg/infusion) during 16 daily 1-hour sessions.ResultsAt 10 μg/kg/infusion nicotine, adolescent rats earned significantly fewer infusions than adults. When responding for 30 μg/kg/infusion nicotine, rats of both ages earned a similar number of infusions; however, there were subtle differences in the distribution of infusions across the 1-hour session. No sex differences were apparent in either age group at any dose.ConclusionsThese results demonstrate that adolescent rats are less sensitive than adults to the primary reinforcing effects of nicotine. However, at nicotine doses that support self-administration in both age groups, adolescent and adult rats do not differ in acquisition or number of infusions earned. These results suggest that reducing nicotine levels in cigarettes to a level that does not support smoking in adults may be sufficient to reduce the acquisition of smoking in adolescents.ImplicationsThe results of the present studies demonstrate that adolescent rats are less sensitive than adults to the primary reinforcing effects of nicotine. These results suggest that reducing nicotine levels in cigarettes to a level that does not support smoking in adults will be sufficient to reduce the acquisition of smoking in adolescents.

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Non-nicotine constituents in e-cigarette aerosol extract attenuate nicotine's aversive effects in adolescent rats.

Publications

Non-nicotine constituents in e-cigarette aerosol extract attenuate nicotine's aversive effects in adolescent rats.

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