{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:52:59Z","timestamp":1783403579556,"version":"3.54.6"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Although nicotine is the primary component of interest in tobacco, the other ~9500 constituents in tobacco are thought to interact with nicotine to contribute to the pharmacological effects relevant to tobacco use disorder. These other tobacco constituents may also contribute to providing an interoceptive stimulus unique from that of nicotine alone. Using a Pavlovian drug discrimination task, we assessed whether rats could discriminate between nicotine and cigarette smoke extract (CSE) of the same nicotine concentration (0.2\u00a0mg\/kg) based on the presence of constituent chemicals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rats were assigned to one of three training conditions in which intermixed daily injections were administered before chamber placement. The interoceptive stimulus elicited by the injected compound would set the occasion on which a light conditioned stimulus would, or would not, be followed by sucrose. Increased dipper entries during the conditioned stimulus indicate greater anticipation of impending sucrose. Groups included (1) nicotine versus vehicle with nicotine signaling sucrose, (2) CSE versus vehicle with CSE signaling sucrose, and (3) CSE versus nicotine with CSE signaling sucrose. This final group determined whether rats could discriminate based on other tobacco constituents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Subjects readily discriminated between nicotine and vehicle and between CSE and vehicle within ~20 training sessions; however, they were unable to discriminate between CSE and nicotine after 72 sessions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results confirm that CSE is a successful Pavlovian discriminative stimulus and add to previous nicotine literature. Interestingly, we demonstrate that CSE and nicotine do not create distinct interoceptive environments under current training conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Implications<\/jats:title>\n                    <jats:p>Nicotine has long been used as a proxy for tobacco in non-human animal studies. However, there has always been an undercurrent regarding the appropriateness of this approach given the myriad constituents in tobacco. Though generalization to other behavioral preparations must be done with extreme caution, the current findings suggest that, at least in some capacity, there is overlap in the stimulus characteristics of nicotine and CSE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ntr\/ntaf219","type":"journal-article","created":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T12:42:15Z","timestamp":1761568935000},"page":"783-790","source":"Crossref","is-referenced-by-count":1,"title":["Cigarette Smoke Extract and Nicotine Evoke Similar Interoceptive Effects in a Pavlovian Occasion Setting Task in Male and Female Sprague\u2013Dawley Rats"],"prefix":"10.1093","volume":"28","author":[{"given":"Anita","family":"Sikic","sequence":"first","affiliation":[{"name":"Department of Psychology, University of Guelph , Guelph, ON ,","place":["Canada"]},{"name":"Collaborative Neurosciences Graduate Program, University of Guelph , Guelph, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davin R","family":"Peart","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Guelph , Guelph, ON ,","place":["Canada"]},{"name":"Collaborative Neurosciences Graduate Program, University of Guelph , Guelph, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mckenna A","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of Guelph , Guelph, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avery R","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Guelph , ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M","family":"Karlovcec","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, University of Guelph , Guelph, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon W","family":"Florek","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Guelph , Guelph, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jude A","family":"Frie","sequence":"additional","affiliation":[{"name":"Collaborative Neurosciences Graduate Program, University of Guelph , Guelph, ON ,","place":["Canada"]},{"name":"Department of Biomedical Sciences, University of Guelph , ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jibran Y","family":"Khokhar","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Western Ontario , London, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick A","family":"Bevins","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Nebraska \u2013 Lincoln , Lincoln, NE ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8992-7317","authenticated-orcid":false,"given":"Jennifer E","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Guelph , Guelph, ON ,","place":["Canada"]},{"name":"Collaborative Neurosciences Graduate Program, University of Guelph , Guelph, ON ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"2026042213023123900_ref1","volume-title":"WHO Report on the Global Tobacco Epidemic, 2023: Protect People from Tobacco Smoke","author":"World Health Organization","year":"2023"},{"key":"2026042213023123900_ref2","volume-title":"Canadian Tobacco and Nicotine Survey (CTNS): Summary of Results for 2022","author":"Health Canada","year":"2023"},{"issue":"5","key":"2026042213023123900_ref3","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1021\/cr50029a004","article-title":"The chemical constituents of tobacco and tobacco smoke","volume":"59","author":"Johnstone","year":"1959","journal-title":"Chem Rev"},{"key":"2026042213023123900_ref4","volume-title":"The Chemical Components of Tobacco and Tobacco Smoke","author":"Rodgman","year":"2013"},{"issue":"4","key":"2026042213023123900_ref5","doi-asserted-by":"publisher","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":"10","key":"2026042213023123900_ref6","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1017\/s1461145709000273","article-title":"The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats","volume":"12","author":"Clemens","year":"2009","journal-title":"Int J Neuropsychopharmacol"},{"issue":"38","key":"2026042213023123900_ref7","doi-asserted-by":"publisher","first-page":"8593","DOI":"10.1523\/jneurosci.2139-05.2005","article-title":"Monoamine oxidase inhibition dramatically increases the motivation to self-administer nicotine in rats","volume":"25","author":"Guillem","year":"2005","journal-title":"J Neurosci"},{"key":"2026042213023123900_ref8","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.drugalcdep.2015.06.005","article-title":"Effects of nicotine and minor tobacco alkaloids on intracranial-self-stimulation in rats","volume":"153","author":"Harris","year":"2015","journal-title":"Drug Alcohol Depend"},{"issue":"8","key":"2026042213023123900_ref9","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1038\/npp.2014.31","article-title":"Comparison of the reinforcing properties of nicotine and cigarette smoke extract in rats","volume":"39","author":"Costello","year":"2014","journal-title":"Neuropsychopharmacology."},{"key":"2026042213023123900_ref10","doi-asserted-by":"publisher","first-page":"1096213","DOI":"10.3389\/fpsyt.2023.1096213","article-title":"Impact of tobacco smoke constituents on nicotine-seeking behavior in adolescent and adult male rats","volume":"14","author":"Gellner","year":"2023","journal-title":"Front Psychiatry"},{"key":"2026042213023123900_ref11","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.neuropharm.2016.06.026","article-title":"Self-administration of nicotine and cigarette smoke extract in adolescent and adult rats","volume":"109","author":"Gellner","year":"2016","journal-title":"Neuropharmacology."},{"key":"2026042213023123900_ref12","doi-asserted-by":"publisher","first-page":"109073","DOI":"10.1016\/j.drugalcdep.2021.109073","article-title":"Self-administration by female rats of low doses of nicotine alone vs. nicotine in tobacco smoke extract","volume":"228","author":"Levin","year":"2021","journal-title":"Drug Alcohol Depend"},{"issue":"1","key":"2026042213023123900_ref13","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3758\/bf03197860","article-title":"Higher order occasion setting","volume":"19","author":"Arnold","year":"1991","journal-title":"Anim Learn Behav"},{"issue":"2","key":"2026042213023123900_ref14","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1037\/bne0000306","article-title":"Occasion setting","volume":"133","author":"Fraser","year":"2019","journal-title":"Behav Neurosci"},{"key":"2026042213023123900_ref15","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/s0079-7421(08)60488-0","article-title":"Occasion setting in Pavlovian conditioning","volume":"28","author":"Holland","year":"1992","journal-title":"Psychol Learn Motiv"},{"issue":"4","key":"2026042213023123900_ref16","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.pbb.2007.03.013","article-title":"The interoceptive Pavlovian stimulus effects of caffeine","volume":"86","author":"Murray","year":"2007","journal-title":"Pharmacol Biochem Behav"},{"issue":"4","key":"2026042213023123900_ref17","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1016\/0091-3057(94)90249-6","article-title":"Drug discrimination using a Pavlovian conditional discrimination paradigm in pigeons","volume":"49","author":"Parker","year":"1994","journal-title":"Pharmacol Biochem Behav"},{"issue":"4","key":"2026042213023123900_ref18","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1037\/1064-1297.12.4.237","article-title":"The discriminative stimulus effects of cocaine in a pavlovian sexual approach paradigm in male Japanese quail","volume":"12","author":"Troisi","year":"2004","journal-title":"Exp Clin Psychopharmacol"},{"issue":"4","key":"2026042213023123900_ref19","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1038\/sj.npp.1300629","article-title":"Stimulus properties of nicotine, amphetamine, and chlordiazepoxide as positive features in a pavlovian appetitive discrimination task in rats","volume":"30","author":"Palmatier undefined","year":"2005","journal-title":"Neuropsychopharmacology."},{"key":"2026042213023123900_ref20","doi-asserted-by":"publisher","first-page":"173173","DOI":"10.1016\/j.pbb.2021.173173","article-title":"Sex differences in the discriminative stimulus characteristics of a morphine occasion setter in rats","volume":"205","author":"Andrade","year":"2021","journal-title":"Pharmacol Biochem Be"},{"issue":"6","key":"2026042213023123900_ref21","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1097\/fbp.0000000000000741","article-title":"Serial feature positive and feature negative discrimination learning in a taste avoidance preparation: implications for interoceptive control of behavior","volume":"34","author":"Huang","year":"2023","journal-title":"Behav Pharmacol"},{"key":"2026042213023123900_ref22","doi-asserted-by":"publisher","first-page":"105541","DOI":"10.1016\/j.yhbeh.2024.105541","article-title":"Generalization of a positive-feature interoceptive morphine occasion setter across the rat estrous cycle","volume":"162","author":"Peart","year":"2024","journal-title":"Horm Behav"},{"issue":"8","key":"2026042213023123900_ref23","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1007\/s00213-024-06584-y","article-title":"Disruption of positive- and negative-feature morphine interoceptive occasion setters by dopamine receptor agonism and antagonism in male and female rats","volume":"241","author":"Peart","year":"2024","journal-title":"Psychopharmacology."},{"issue":"8","key":"2026042213023123900_ref24","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1007\/s00213-020-05542-8","article-title":"Menthol blunts the interoceptive discriminative stimulus effects of nicotine in female but not male rats","volume":"237","author":"Huynh","year":"2020","journal-title":"Psychopharmacology."},{"issue":"3","key":"2026042213023123900_ref25","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1097\/01.fbp.0000132915.11693.8e","article-title":"Nicotine serves as a feature-positive modulator of Pavlovian appetitive conditioning in rats","volume":"15","author":"Palmatier","year":"2004","journal-title":"Behav Pharmacol"},{"issue":"3-4","key":"2026042213023123900_ref26","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1007\/s00213-005-0079-3","article-title":"Characterization of nicotine\u2019s ability to serve as a negative feature in a Pavlovian appetitive conditioning task in rats","volume":"184","author":"Bevins","year":"2006","journal-title":"Psychopharmacology."},{"key":"2026042213023123900_ref27","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.bbr.2016.01.011","article-title":"Nicotine administration enhances negative occasion setting in adolescent rats","volume":"302","author":"Meyer","year":"2016","journal-title":"Behav Brain Res"},{"key":"2026042213023123900_ref28","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.neuropharm.2014.10.025","article-title":"Inhibitory learning is modulated by nicotinic acetylcholine receptors","volume":"89","author":"Meyer","year":"2015","journal-title":"Neuropharmacology."},{"issue":"7","key":"2026042213023123900_ref29","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1101\/lm.2177411","article-title":"Nicotine trained as a negative feature passes the retardation-of- acquisition and summation tests of a conditioned inhibitor","volume":"18","author":"Murray","year":"2011","journal-title":"Learn Mem"},{"key":"2026042213023123900_ref30","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.bbr.2016.03.029","article-title":"Differential discriminative-stimulus effects of cigarette smoke condensate and nicotine in nicotine-discriminating rats","volume":"306","author":"Lee","year":"2016","journal-title":"Behav Brain Res"},{"issue":"2","key":"2026042213023123900_ref31","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1097\/01.fbp.0000197456.63150.cd","article-title":"Interoceptive Pavlovian conditioning with nicotine as the conditional stimulus varies as a function of the number of conditioning trials and unpaired sucrose deliveries","volume":"17","author":"Wilkinson","year":"2006","journal-title":"Behav Pharmacol"},{"issue":"1-3","key":"2026042213023123900_ref32","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.ejphar.2007.01.046","article-title":"Behavioral and neuropharmacological characterization of nicotine as a conditional stimulus","volume":"561","author":"Murray","year":"2007","journal-title":"Eur J Pharmacol"},{"issue":"8","key":"2026042213023123900_ref33","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1097\/fbp.0b013e3282f14ec6","article-title":"The conditional stimulus effects of nicotine vary as a function of training dose","volume":"18","author":"Murray","year":"2007","journal-title":"Behav Pharmacol"},{"issue":"3","key":"2026042213023123900_ref34","doi-asserted-by":"publisher","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."},{"issue":"1","key":"2026042213023123900_ref35","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.beproc.2009.01.002","article-title":"Nicotine-evoked conditioned responding is dependent on concentration of sucrose unconditioned stimulus","volume":"81","author":"Murray","year":"2009","journal-title":"Behav Process"},{"issue":"1","key":"2026042213023123900_ref36","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1007\/s00213-003-1621-9","article-title":"Nicotine as a signal for the presence or absence of sucrose reward: a Pavlovian drug appetitive conditioning preparation in rats","volume":"172","author":"Besheer","year":"2004","journal-title":"Psychopharmacology."},{"issue":"1","key":"2026042213023123900_ref37","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1037\/a0013735","article-title":"Acquired appetitive responding to intravenous nicotine reflects a Pavlovian conditioned association","volume":"123","author":"Murray","year":"2009","journal-title":"Behav Neurosci"},{"key":"2026042213023123900_ref38","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.pbb.2014.02.011","article-title":"Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats","volume":"120","author":"Hall","year":"2014","journal-title":"Pharmacol Biochem Behav"},{"key":"2026042213023123900_ref39","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.drugalcdep.2015.07.002","article-title":"Effects of MAO inhibition and a combination of minor alkaloids, \u03b2-carbolines, and acetaldehyde on nicotine self-administration in adult male rats","volume":"155","author":"Smith","year":"2015","journal-title":"Drug Alcohol Depend"},{"issue":"5","key":"2026042213023123900_ref40","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1111\/j.1460-9568.2006.05011.x","article-title":"Irreversible blockade of monoamine oxidases reveals the critical role of 5-HT transmission in locomotor response induced by nicotine in mice","volume":"24","author":"Vill\u00e9gier","year":"2006","journal-title":"Eur J Neurosci"},{"issue":"5","key":"2026042213023123900_ref41","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1093\/ntr\/ntv245","article-title":"Contribution of monoamine oxidase inhibition to tobacco dependence: a review of the evidence","volume":"18","author":"Hogg","year":"2016","journal-title":"Nicotine Tob 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\/ntaf219\/65024030\/ntaf219.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ntr\/article-pdf\/28\/5\/783\/65024030\/ntaf219.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ntr\/article-pdf\/28\/5\/783\/65024030\/ntaf219.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T17:02:38Z","timestamp":1776877358000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ntr\/article\/28\/5\/783\/8305736"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,29]]},"references-count":41,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,10,29]]},"published-print":{"date-parts":[[2026,4,22]]}},"URL":"https:\/\/doi.org\/10.1093\/ntr\/ntaf219","relation":{},"ISSN":["1469-994X"],"issn-type":[{"value":"1469-994X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2025,10,29]]}}}