{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T03:08:20Z","timestamp":1791256100937,"version":"4.1.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T00:00:00Z","timestamp":1718755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Key Laboratory of Tobacco Biological Effects","award":["552018AQ0090"],"award-info":[{"award-number":["552018AQ0090"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The distinctions in the biological impacts of distinct forms of nicotine have become a prominent subject of current research. However, relatively little research has been done on the addictive effects of different forms of nicotine.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Aims and Methods<\/jats:title>\n                  <jats:p>The aerosol self-administration device was briefly characterized by determining aerosol concentration, particle size, and distributional diffusion of the aerosol. And the aerosol self-administration model was constructed at 1, 5, and 10 mg\/mL of nicotine to select the appropriate nicotine concentration. Subsequently, the model was used to explore the differences in aerosol self-administration behavior of free-base nicotine and nicotine salts and the behavioral differences after withdrawal.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We successfully constructed mouse aerosol self-administration models at 1, 5, and 10 mg\/mL nicotine concentrations. In the study of the difference in addictive behaviors between free-base nicotine and nicotine salts, mice with free-base nicotine and different nicotine salts showed varying degrees of drug-seeking behavior, with nicotine benzoate showing the strongest reinforcement. In post-withdrawal behavioral experiments, nicotine salts mice showed more robust anxiety-like behaviors.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These results confirm the successful development and stability of the nicotine aerosol self-administration model. Furthermore, they demonstrated that nicotine salts enhance drug-seeking behavior to a greater extent than free-base nicotine, with nicotine benzoate exhibiting the most significant effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Implications<\/jats:title>\n                  <jats:p>In this study, an aerosol self-administered model of mice was constructed, which can be used not only for comparing the effects of free-base nicotine and nicotine salts on the behavior but also for other addictive drugs, such as fentanyl and cannabis. In addition, this study shows that nicotine salts may be more addictive compared to free-base nicotine, which is a reference for the future use of nicotine salts in tobacco products such as e-cigarettes.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ntr\/ntae150","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T05:36:22Z","timestamp":1718775382000},"page":"1626-1635","source":"Crossref","is-referenced-by-count":6,"title":["The Difference of Addictive Behavior of Free-Base Nicotine and Nicotine Salts in Mice Base on an Aerosol Self-Administration Model"],"prefix":"10.1093","volume":"26","author":[{"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Research Division 1, Beijing Life Science Academy , Beijing ,","place":["China"]},{"name":"Risk Assessment Team, Key Laboratory of Tobacco Biological Effects , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shulei","family":"Han","sequence":"additional","affiliation":[{"name":"Research Division 1, Beijing Life Science Academy , Beijing ,","place":["China"]},{"name":"Risk Assessment Team, Key Laboratory of Tobacco Biological Effects , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Fan","sequence":"additional","affiliation":[{"name":"Research Division 1, Beijing Life Science Academy , Beijing ,","place":["China"]},{"name":"Risk Assessment Team, Key Laboratory of Tobacco Biological Effects , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanglin","family":"Liu","sequence":"additional","affiliation":[{"name":"Research Division 1, Beijing Life Science Academy , Beijing ,","place":["China"]},{"name":"Risk Assessment Team, Key Laboratory of Tobacco Biological Effects , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Research Division 1, Beijing Life Science Academy , Beijing ,","place":["China"]},{"name":"Risk Assessment Team, Key Laboratory of Tobacco Biological Effects , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Chen","sequence":"additional","affiliation":[{"name":"Research Division 1, Beijing Life Science Academy , Beijing ,","place":["China"]},{"name":"Risk Assessment Team, Key Laboratory of Tobacco Biological Effects , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9389-4928","authenticated-orcid":false,"given":"Hongwei","family":"Hou","sequence":"additional","affiliation":[{"name":"Research Division 1, Beijing Life Science Academy , Beijing ,","place":["China"]},{"name":"Risk Assessment Team, Key Laboratory of Tobacco Biological Effects , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Research Division 1, Beijing Life Science Academy , Beijing ,","place":["China"]},{"name":"Risk Assessment Team, Key Laboratory of Tobacco Biological Effects , Zhengzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,6,19]]},"reference":[{"issue":"1","key":"2024112205514070100_CIT0001","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41572-022-00346-w","article-title":"Tobacco and nicotine use","volume":"8","author":"Le Foll","year":"2022","journal-title":"Nat Rev Dis Primers."},{"issue":"1","key":"2024112205514070100_CIT0002","doi-asserted-by":"crossref","first-page":"e20163436","DOI":"10.1542\/peds.2016-3436","article-title":"Nicotine and tobacco as substances of abuse in children and adolescents","volume":"139","author":"Siqueira","year":"2017","journal-title":"Pediatrics."},{"issue":"12","key":"2024112205514070100_CIT0003","doi-asserted-by":"crossref","first-page":"e012742","DOI":"10.1161\/JAHA.119.012742","article-title":"Is there a role for electronic cigarettes in tobacco cessation","volume":"8","author":"Bhatnagar","year":"2019","journal-title":"J Am Heart Assoc"},{"issue":"2","key":"2024112205514070100_CIT0004","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1177\/2042098614524430","article-title":"Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review","volume":"5","author":"Farsalinos","year":"2014","journal-title":"Ther Adv Drug Saf"},{"issue":"7","key":"2024112205514070100_CIT0005","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1093\/ntr\/ntz232","article-title":"Characterization of nicotine salts in 23 electronic cigarette refill liquids","volume":"22","author":"Harvanko","year":"2020","journal-title":"Nicotine Tob Res."},{"issue":"1","key":"2024112205514070100_CIT0006","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s002130050542","article-title":"Acquisition of nicotine self-administration in rats: the effects of dose, feeding schedule, and drug contingency","volume":"136","author":"Donny","year":"1998","journal-title":"Psychopharmacology (Berl)."},{"issue":"4","key":"2024112205514070100_CIT0007","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1152\/japplphysiol.00717.2019","article-title":"Pod-mod vs. conventional e-cigarettes: nicotine chemistry, pH, and health effects","volume":"128","author":"Shao","year":"2020","journal-title":"J Appl Physiol."},{"key":"2024112205514070100_CIT0008","doi-asserted-by":"crossref","first-page":"108732","DOI":"10.1016\/j.drugalcdep.2021.108732","article-title":"Nicotine formulations impact reinforcement-related behaviors in a mouse model of vapor self-administration","volume":"224","author":"Henderson","year":"2021","journal-title":"Drug Alcohol Depend."},{"key":"2024112205514070100_CIT0009","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1080\/17425247.2020.1814736","article-title":"Nicotine forms: why and how do they matter in nicotine delivery from electronic cigarettes","volume":"17(12)","author":"Gholap","year":"2020","journal-title":"Expert Opin Drug Deliv."},{"key":"2024112205514070100_CIT0010","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.forsciint.2018.05.042","article-title":"Abuse of fentanyl: an emerging problem to face","volume":"289","author":"Kuczy\u0144ska","year":"2018","journal-title":"Forensic Sci Int."},{"issue":"4","key":"2024112205514070100_CIT0011","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/sj.npp.1300586","article-title":"Acetaldehyde enhances acquisition of nicotine self-administration in adolescent rats","volume":"30","author":"Belluzzi","year":"2005","journal-title":"Neuropsychopharmacology."},{"issue":"4","key":"2024112205514070100_CIT0012","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1111\/adb.12021","article-title":"Nicotine vapor inhalation escalates nicotine self-administration","volume":"19","author":"Gilpin","year":"2014","journal-title":"Addict Biol."},{"key":"2024112205514070100_CIT0013","first-page":"8.41.1\u20138.41.10","article-title":"Nicotine vapor method to induce nicotine dependence in rodents","volume":"80","author":"Kallupi","year":"2017","journal-title":"Curr Protoc Neurosci"},{"issue":"32","key":"2024112205514070100_CIT0014","doi-asserted-by":"crossref","first-page":"eabc0413","DOI":"10.1126\/sciadv.abc0413","article-title":"Fentanyl vapor self-administration model in mice to study opioid addiction","volume":"6","author":"Moussawi","year":"2020","journal-title":"Sci Adv."},{"issue":"9","key":"2024112205514070100_CIT0015","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1523\/JNEUROSCI.2416-19.2020","article-title":"Vaporized cannabis extracts have reinforcing properties and support conditioned drug-seeking behavior in rats","volume":"40","author":"Freels","year":"2020","journal-title":"J Neurosci."},{"issue":"3","key":"2024112205514070100_CIT0016","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.alcohol.2013.08.006","article-title":"Operant alcohol self-administration in dependent rats: focus on the vapor model","volume":"48","author":"Vendruscolo","year":"2014","journal-title":"Alcohol."},{"issue":"13","key":"2024112205514070100_CIT0017","doi-asserted-by":"crossref","first-page":"2009","DOI":"10.1007\/s00213-017-4608-7","article-title":"Voluntary induction and maintenance of alcohol dependence in rats using alcohol vapor self-administration","volume":"234","author":"de Guglielmo","year":"2017","journal-title":"Psychopharmacology (Berl)."},{"issue":"7","key":"2024112205514070100_CIT0018","doi-asserted-by":"crossref","first-page":"e67674","DOI":"10.1371\/journal.pone.0067674","article-title":"Menthol binding and inhibition of \u03b17-nicotinic acetylcholine receptors","volume":"8","author":"Ashoor","year":"2013","journal-title":"PLoS One."},{"issue":"5","key":"2024112205514070100_CIT0019","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/chemse\/bjr128","article-title":"Menthol suppresses nicotinic acetylcholine receptor functioning in sensory neurons via allosteric modulation","volume":"37","author":"Hans","year":"2012","journal-title":"Chem Senses."},{"issue":"5","key":"2024112205514070100_CIT0020","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1017\/S1461145712001022","article-title":"Up-regulation of nicotinic acetylcholine receptors in menthol cigarette smokers","volume":"16","author":"Brody","year":"2013","journal-title":"Int J Neuropsychopharmacol."},{"issue":"12","key":"2024112205514070100_CIT0021","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1038\/npp.2017.72","article-title":"Menthol enhances nicotine reward-related behavior by potentiating nicotine-induced changes in nAChR function, nAChR upregulation, and DA neuron excitability","volume":"42","author":"Henderson","year":"2017","journal-title":"Neuropsychopharmacology."},{"issue":"9","key":"2024112205514070100_CIT0022","doi-asserted-by":"crossref","first-page":"e0137070","DOI":"10.1371\/journal.pone.0137070","article-title":"Effects of menthol on nicotine pharmacokinetic, pharmacology and dependence in mice","volume":"10","author":"Alsharari","year":"2015","journal-title":"PLoS One."},{"issue":"2","key":"2024112205514070100_CIT0023","doi-asserted-by":"crossref","first-page":"e0117128","DOI":"10.1371\/journal.pone.0117128","article-title":"Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice","volume":"10","author":"Ha","year":"2015","journal-title":"PLoS One."},{"key":"2024112205514070100_CIT0024","first-page":"1099","article-title":"Pharmacokinetics of freebase nicotine and nicotine salts following subcutaneous administration in male rats","volume":"15(10)","author":"Han","year":"2022","journal-title":"Drug Test Anal."},{"key":"2024112205514070100_CIT0025","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-1-4939-8994-2_9","article-title":"The open field test for measuring locomotor activity and anxiety-like behavior","volume":"1916","author":"Kraeuter","year":"2019","journal-title":"Methods Mol Biol."},{"key":"2024112205514070100_CIT0026","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1007\/978-1-4939-8994-2_4","article-title":"The elevated plus maze test for measuring anxiety-like behavior in rodents","volume":"1916","author":"Kraeuter","year":"2019","journal-title":"Methods Mol Biol."},{"issue":"11","key":"2024112205514070100_CIT0027","doi-asserted-by":"crossref","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":"2020","journal-title":"Neuropsychopharmacology."},{"key":"2024112205514070100_CIT0028","doi-asserted-by":"crossref","first-page":"925272","DOI":"10.3389\/fnmol.2022.925272","article-title":"Harmane potentiates nicotine reinforcement through MAO-A inhibition at the dose related to cigarette smoking","volume":"15","author":"Ding","year":"2022","journal-title":"Front Mol Neurosci."},{"key":"2024112205514070100_CIT0029","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/978-3-319-13482-6_4","article-title":"Nicotine withdrawal","volume-title":"The Neuropharmacology of Nicotine Dependence","author":"McLaughlin","year":"2015"},{"issue":"6","key":"2024112205514070100_CIT0030","doi-asserted-by":"crossref","first-page":"e13024","DOI":"10.1111\/adb.13024","article-title":"Nicotine e-cigarette vapor inhalation and self-administration in a rodent model: sex- and nicotine delivery-specific effects on metabolism and behavior","volume":"26","author":"Lallai","year":"2021","journal-title":"Addict Biol."},{"key":"2024112205514070100_CIT0031","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.fct.2018.01.045","article-title":"Particle size distribution of selected electronic nicotine delivery system products","volume":"113","author":"Oldham","year":"2018","journal-title":"Food Chem Toxicol."},{"issue":"5","key":"2024112205514070100_CIT0032","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1152\/japplphysiol.00357.2018","article-title":"Chronic intermittent nicotine delivery via lung alveolar region-targeted aerosol technology produces circadian pharmacokinetics in rats resembling human smokers","volume":"125","author":"Shao","year":"2018","journal-title":"J Appl Physiol."},{"issue":"5","key":"2024112205514070100_CIT0033","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1037\/pha0000140","article-title":"Electronic cigarette user plasma nicotine concentration, puff topography, heart rate, and subjective effects: influence of liquid nicotine concentration and user experience","volume":"25","author":"Hiler","year":"2017","journal-title":"Exp Clin Psychopharmacol."},{"issue":"3","key":"2024112205514070100_CIT0034","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s00213-019-05400-2","article-title":"Nicotine e-cigarette vapor inhalation effects on nicotine & cotinine plasma levels and somatic withdrawal signs in adult male Wistar rats","volume":"237","author":"Montanari","year":"2020","journal-title":"Psychopharmacology (Berl)."},{"issue":"4","key":"2024112205514070100_CIT0035","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1007\/s00429-015-1014-y","article-title":"Impact of prenatal nicotine on the structure of midbrain dopamine regions in the rat","volume":"221","author":"Omelchenko","year":"2016","journal-title":"Brain Struct Funct."},{"key":"2024112205514070100_CIT0036","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev.pharmtox.48.113006.094742","article-title":"Pharmacology of nicotine: addiction, smoking-induced disease, and therapeutics","volume":"49","author":"Benowitz","year":"2009","journal-title":"Annu Rev Pharmacol Toxicol."},{"issue":"3","key":"2024112205514070100_CIT0037","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1124\/mol.106.032086","article-title":"Characterization and comparison of nicotine and cotinine metabolism in vitro and in vivo in DBA\/2 and C57BL\/6 mice","volume":"71","author":"Siu","year":"2007","journal-title":"Mol Pharmacol."},{"issue":"3","key":"2024112205514070100_CIT0038","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s00213-006-0441-0","article-title":"Guidelines on nicotine dose selection for in vivo research","volume":"190","author":"Matta","year":"2007","journal-title":"Psychopharmacology (Berl)."},{"key":"2024112205514070100_CIT0039","article-title":"The role of nicotine metabolic rate on nicotine dependence and rewarding: nicotine metabolism in Chinese male smokers and male mice","author":"Liu","year":"2024","journal-title":"Mol Neurobiol."},{"issue":"1","key":"2024112205514070100_CIT0040","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1124\/jpet.106.111237","article-title":"Inhibition of nicotine metabolism by methoxysalen: pharmacokinetic and pharmacological studies in mice","volume":"320","author":"Damaj","year":"2007","journal-title":"J Pharmacol Exp Ther."},{"issue":"1","key":"2024112205514070100_CIT0041","doi-asserted-by":"crossref","first-page":"e2032757","DOI":"10.1001\/jamanetworkopen.2020.32757","article-title":"Effect of exposure to e-cigarettes with salt vs free-base nicotine on the appeal and sensory experience of vaping: a randomized clinical trial","volume":"4","author":"Leventhal","year":"2021","journal-title":"JAMA Netw Open"},{"issue":"4","key":"2024112205514070100_CIT0042","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1016\/j.neuropharm.2011.05.012","article-title":"Intravenous nicotine self-administration and cue-induced reinstatement in mice: effects of nicotine dose, rate of drug infusion and prior instrumental training","volume":"61","author":"Fowler","year":"2011","journal-title":"Neuropharmacology."},{"issue":"6 pt 1","key":"2024112205514070100_CIT0043","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/S0013-7006(06)76275-3","article-title":"Heritability and candidate genes in tobacco use","volume":"32","author":"Hamdani","year":"2006","journal-title":"L\u2019Encephale"},{"issue":"1","key":"2024112205514070100_CIT0044","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.bbr.2005.09.003","article-title":"Individual differences in novelty-seeking behavior but not in anxiety response to a new environment can predict nicotine consumption in adolescent C57BL\/6 mice","volume":"167","author":"Abreu-Villa\u00e7a","year":"2006","journal-title":"Behav Brain Res."},{"key":"2024112205514070100_CIT0045","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.pbb.2015.02.009","article-title":"Nicotine withdrawal in selectively bred high and low nicotine preferring rat lines","volume":"131","author":"Nesil","year":"2015","journal-title":"Pharmacol Biochem Behav."},{"issue":"1\u20132","key":"2024112205514070100_CIT0046","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1002\/jnr.23858","article-title":"Sex differences in nicotine preference","volume":"95","author":"Pogun","year":"2017","journal-title":"J Neurosci Res."}],"container-title":["Nicotine and Tobacco Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ntr\/advance-article-pdf\/doi\/10.1093\/ntr\/ntae150\/58604292\/ntae150.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ntr\/article-pdf\/26\/12\/1626\/59834689\/ntae150.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ntr\/article-pdf\/26\/12\/1626\/59834689\/ntae150.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T05:53:23Z","timestamp":1732254803000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ntr\/article\/26\/12\/1626\/7695974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,19]]},"references-count":46,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,6,19]]},"published-print":{"date-parts":[[2024,11,22]]}},"URL":"https:\/\/doi.org\/10.1093\/ntr\/ntae150","relation":{},"ISSN":["1469-994X"],"issn-type":[{"value":"1469-994X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,12]]},"published":{"date-parts":[[2024,6,19]]}}}