{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:01:13Z","timestamp":1790146873209,"version":"4.0.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Propylene glycol (PG) and glycerol (Gly) are odorless tobacco product constituents that act as solvents in electronic cigarette e-liquids and as humectants in oral nicotine products. Little is known about how PG\/Gly ratio may affect nicotine\u2019s sensory and rewarding properties. To address this gap, we utilized the taste reactivity test and four-bottle choice test to investigate the impact of PG\/Gly ratio on nicotine\u2019s taste and reward.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A taste reactivity test was performed using young adult rats that received oral infusions of water, nicotine (10\u00a0\u03bcg\/mL) and various PG\/Gly ratios in the absence and presence of nicotine via intraoral catheters. Facial responses to each infusion were video recorded and the ingestive and aversive taste responses to each solution were scored and analyzed. In a separate cohort of rats, a four-bottle choice test was utilized to assess preference for various PG\/Gly ratios with or without nicotine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Young adult rats exhibited higher aversive reactions to PG100\/Gly0 alone. Higher Gly content (PG0\/Gly100 with nicotine) increased ingestive responses compared to nicotine alone. Higher Gly content (PG20\/Gly80 with nicotine and PG0\/Gly100 with nicotine) decreased aversive reactions compared to nicotine alone. Young adult rats also displayed greater preference for PG0\/Gly100 alone and PG0\/Gly100 with nicotine compared to vehicle water and nicotine, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, nicotine\u2019s ingestive and aversive taste was altered by PG and Gly depending on the ratio. Specifically, higher Gly enhanced nicotine\u2019s hedonic value and reduced nicotine\u2019s aversive properties in both sexes. Higher Gly content was also preferred during the four-bottle choice test alone and in the presence of nicotine. Together, our results suggests that PG\/Gly ratio, particularly high Gly content, influences nicotine\u2019s abuse liability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1955253","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:16:05Z","timestamp":1790144165000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The ratio of propylene glycol to glycerol modulates nicotine taste and reward: more glycerol, more reward"],"prefix":"10.3389","volume":"17","author":[{"given":"Tyler","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, Yale University","place":["New Haven, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexxis","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, Yale University","place":["New Haven, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Minanov","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, Yale University","place":["New Haven, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merve","family":"Seferge","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, Yale University","place":["New Haven, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nii A.","family":"Addy","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, Yale University","place":["New Haven, CT, United States"]},{"name":"Yale Center for the Study of Tobacco Product Use and Addiction, Yale University","place":["New Haven, CT, United States"]},{"name":"Department of Cellular and Molecular Physiology, Yale School of Medicine, Yale University","place":["New Haven, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Bagdas","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine, Yale University","place":["New Haven, CT, United States"]},{"name":"Yale Center for the Study of Tobacco Product Use and Addiction, Yale University","place":["New Haven, CT, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1093\/ntr\/ntab241","article-title":"Evaluation of flavor effects on oral nicotine liking and\/or disliking using the taste reactivity test in rats","volume":"24","author":"Bagdas","year":"2021","journal-title":"Nicotine Tob. Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2241","DOI":"10.1007\/s00213-024-06630-9","article-title":"Impact of vanilla flavor on nicotine taste, choice, intake, and seeking behaviors","volume":"241","author":"Bagdas","year":"2024","journal-title":"Psychopharmacol. Berl."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2026.01.12.697777","DOI":"10.64898\/2026.01.12.697777","article-title":"Effects of commercial unflavored and vanilla-flavored e-liquids on nicotine intake and withdrawal","author":"Bagdas","year":"","journal-title":"bioRxiv"},{"key":"B4","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1093\/ntr\/ntaf037","article-title":"Effects of sweeteners and cinnamon flavor on oral nicotine choice behaviors","volume":"28","author":"Bagdas","year":"","journal-title":"Nicotine Tob. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"475","DOI":"10.15585\/mmwr.mm7218a1","article-title":"Tobacco product use among adults - United States, 2021","volume":"72","author":"Cornelius","year":"2023","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1161\/CIR.0000000000001293","article-title":"Impact of smokeless oral nicotine products on cardiovascular disease: implications for policy, prevention, and treatment: a policy statement from the American heart association","volume":"151","author":"Dennison Himmelfarb","year":"2025","journal-title":"Circulation"},{"key":"B7","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s12954-020-00420-0","article-title":"Sensory experiences and cues among E-cigarette users","volume":"17","author":"DiPiazza","year":"2020","journal-title":"Harm Reduct. J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1093\/ntr\/ntac073","article-title":"The role of nicotine and flavor in the abuse potential and appeal of electronic cigarettes for adult current and former cigarette and electronic cigarette users: a systematic review","volume":"24","author":"Gades","year":"2022","journal-title":"Nicotine Tob. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.drugalcdep.2016.09.014","article-title":"Effects of sweet flavorings and nicotine on the appeal and sensory properties of e-cigarettes among young adult vapers: application of a novel methodology","volume":"168","author":"Goldenson","year":"2016","journal-title":"Drug Alcohol Dependence"},{"key":"B10","doi-asserted-by":"crossref","DOI":"10.64898\/2026.04.16.719070","volume-title":"Chronic Pain Exacerbates Nicotine Withdrawal Severity in a Sex-specific and Dose-dependent Manner","author":"Graham","year":"2026"},{"key":"B11","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/0006-8993(78)90568-1","article-title":"The taste reactivity test. I. Mimetic responses to gustatory stimuli in neurologically normal rats","volume":"143","author":"Grill","year":"1978","journal-title":"Brain Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"168","DOI":"10.18001\/TRS.3.2.4","article-title":"Flavored tobacco product use among youth and young adults: what if flavors didn\u2019t exist?","volume":"3","author":"Harrell","year":"2017","journal-title":"Tob. Regul. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.addbeh.2018.04.009","article-title":"Electronic cigarette liquid and device parameters and aerosol characteristics: a survey of regular users","volume":"84","author":"Harvanko","year":"2018","journal-title":"Addict. Behav."},{"key":"B14","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.drugalcdep.2018.08.039","article-title":"Stimulus effects of propylene glycol and vegetable glycerin in electronic cigarette liquids","volume":"194","author":"Harvanko","year":"2019","journal-title":"Drug Alcohol Dependence"},{"key":"B15","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/0006-8993(76)90860-x","article-title":"Stimulation of the gerbil\u2019s gustatory receptors by monosaccharides","volume":"110","author":"Jakinovich","year":"1976","journal-title":"Brain Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"917","DOI":"10.15585\/mmwr.mm7341a2","article-title":"Tobacco product use among middle and high school students - national youth tobacco survey, United States, 2024","volume":"73","author":"Jamal","year":"2024","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1093\/ntr\/ntu243","article-title":"E-cigarette use among high school and middle school adolescents in Connecticut","volume":"17","author":"Krishnan-Sarin","year":"2015","journal-title":"Nicotine Tob. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"134567","DOI":"10.1016\/j.scitotenv.2019.134567","article-title":"Quantitative insights into major constituents contained in or released by electronic cigarettes: propylene glycol, vegetable glycerin, and nicotine","volume":"703","author":"Lee","year":"2020","journal-title":"Sci. Total Environ."},{"key":"B19","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.drugalcdep.2019.05.020","article-title":"Effects of non-tobacco flavors and nicotine on e-cigarette product appeal among young adult never, former, and current smokers","volume":"203","author":"Leventhal","year":"2019","journal-title":"Drug Alcohol Dependence"},{"key":"B20","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1186\/s12889-016-3326-0","article-title":"Analysis of symptoms and their potential associations with e-liquids\u2019 components: a social media study","volume":"16","author":"Li","year":"2016","journal-title":"BMC Public Health"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e0286258","DOI":"10.1371\/journal.pone.0286258","article-title":"The associations between e-liquid characteristics and its pricing: evidence from online vape shops","volume":"18","author":"Ma","year":"2023","journal-title":"PLOS ONE"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1007\/s00204-023-03538-9","article-title":"Oral nicotine pouches with an aftertaste? Part 1: screening and initial toxicological assessment of flavorings and other ingredients","volume":"97","author":"Mallock-Ohnesorg","year":"2023","journal-title":"Arch. Toxicol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1126\/science.184.4136.583","article-title":"Sugar sweetness and pleasantness: evidence for different psychological laws","volume":"184","author":"Moskowitz","year":"1974","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1093\/ntr\/ntae281","article-title":"Appeal and sensory characteristics of oral nicotine products in young adults who vape E-Cigarettes","volume":"28","author":"Peraza","year":"2026","journal-title":"Nicotine Tob. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12078-017-9231-9","article-title":"Pilot experiment: the effect of added flavorants on the taste and pleasantness of mixtures of glycerol and propylene glycol","volume":"11","author":"Rao","year":"2018","journal-title":"Chemosens. Percept."},{"key":"B26","doi-asserted-by":"publisher","first-page":"878976","DOI":"10.3389\/ftox.2022.878976","article-title":"Toxicological assessment of flavor ingredients in E-Vapor products","volume":"4","author":"Sciuscio","year":"2022","journal-title":"Front. Toxicol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1909","DOI":"10.1038\/s41386-020-0734-8","article-title":"Validation of a nicotine vapor self-administration model in rats with relevance to electronic cigarette use","volume":"45","author":"Smith","year":"","journal-title":"Neuropsychopharmacology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1093\/ntr\/ntz130","article-title":"The impact of E-liquid propylene glycol and vegetable glycerin ratio on ratings of subjective effects, reinforcement value, and use in current smokers","volume":"22","author":"Smith","year":"","journal-title":"Nicotine Tob. Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.drugalcdep.2018.03.042","article-title":"Effects of electronic cigarette liquid solvents propylene glycol and vegetable glycerin on user nicotine delivery, heart rate, subjective effects, and puff topography","volume":"188","author":"Spindle","year":"2018","journal-title":"Drug Alcohol Depend."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/02786826.2016.1257853","article-title":"Transport phenomena governing nicotine emissions from electronic cigarettes: model formulation and experimental investigation","volume":"51","author":"Talih","year":"2017","journal-title":"Aerosol Sci. Technol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1093\/ntr\/ntab192","article-title":"Adolescents\u2019 use of nicotine-free and nicotine E-Cigarettes: a longitudinal study of vaping transitions and vaper characteristics","volume":"24","author":"Tokle","year":"2021","journal-title":"Nicotine Tob. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1016\/j.pbb.2009.02.009","article-title":"Hedonic sensitivity in adolescent and adult rats: taste reactivity and voluntary sucrose consumption","volume":"92","author":"Wilmouth","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B33","doi-asserted-by":"publisher","first-page":"102392","DOI":"10.1016\/j.flowmeasinst.2023.102392","article-title":"Experimental investigation on the dynamic behavior and microscopic characteristics of the aerosol produced by ceramic coil atomizer of e-cigarettes","volume":"92","author":"Yang","year":"2023","journal-title":"Flow Meas. Instrum."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1955253\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T06:16:07Z","timestamp":1790144167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1955253\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":33,"alternative-id":["10.3389\/fphar.2026.1955253"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1955253","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]},"article-number":"1955253"}}