{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T22:51:13Z","timestamp":1777762273656,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007197","name":"United States Public Health Services","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007197","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["P50DA046346"],"award-info":[{"award-number":["P50DA046346"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA061227"],"award-info":[{"award-number":["R01DA061227"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R01DA058955"],"award-info":[{"award-number":["R01DA058955"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["CIHR TCP-431510"],"award-info":[{"award-number":["CIHR TCP-431510"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Most substance users are polysubstance users; however, little is known about how the combined use of different drugs affects the course of substance use disorder or effectiveness of treatment. Notably, co-use of cannabis and nicotine is very common, and we previously demonstrated that nicotine enhances the self-administration of a synthetic cannabinoid receptor agonist and the primary psychoactive phytocannabinoid in cannabis, \u0394-9-tetrahydrocannabinol (THC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Here we aimed to further investigate the patterns of nicotine and THC self-administration when available in a concurrent choice model, and to determine the effects of nicotinic acetylcholine receptor (nAchR) antagonists on nicotine-enhanced THC self-administration in male and female rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>During concurrent choice, nicotine availability increased THC self-administration in females without affecting THC metabolism, while THC availability decreased nicotine self-administration and preference in females relative to when nicotine and saline were concurrently available. In females, THC self-administration was reduced by the \u03b14\u03b22\/4 subunit-containing nAchR antagonist dihydro-beta-erythroidine in both nicotine and saline concurrent availability groups; while nicotine self-administration was reduced in both sexes by the \u03b17nAchR antagonist methylylcaconitine, but only in rats that had concurrent access to THC. The nonspecific nAchR antagonist mecamylamine had minimal effects in the concurrent choice model, but it prevented nicotine-induced enhancement of THC self-administration when nicotine was given prior to a single choice THC only self-administration session.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Thus, behavioral regulation of self-administration is differentially influenced by nAchR subtypes depending on the availability of other substances, which has implications for the efficacy of treatments in the context of polysubstance use.<\/jats:p>\n                    <jats:p>Significance statement Polysubstance use is extremely common, but very understudied in both clinical and preclinical research. The results presented here highlight that pharmacological modulators of drug reinforcement can differ when multiple drugs are available simultaneously, highlighting the importance of investigating potential treatments for substance use disorders in the context of polysubstance use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ijnp\/pyag015","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T11:44:45Z","timestamp":1775043885000},"source":"Crossref","is-referenced-by-count":0,"title":["Effects of nicotinic receptor antagonism on nicotine and THC self-administration in a model of polysubstance use"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2083-0231","authenticated-orcid":false,"given":"Mary M","family":"Torregrossa","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Pittsburgh , Pittsburgh, PA 15219 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Racic","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha L","family":"Baglot","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology and Anatomy & Psychiatry, Cumming School of Medicine, Hotchkiss Brain Institute and The Mathison Centre for Mental Health Research and Education, University of Calgary , Calgary ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4840-0866","authenticated-orcid":false,"given":"Sierra J","family":"Stringfield","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew N","family":"Hill","sequence":"additional","affiliation":[{"name":"Departments of Cell Biology and Anatomy & Psychiatry, Cumming School of Medicine, Hotchkiss Brain Institute and The Mathison Centre for Mental Health Research and Education, University of Calgary , Calgary ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Sved","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Pittsburgh , Pittsburgh, PA 15213 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"2026042910265709100_ref1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.drugalcdep.2018.07.025","article-title":"The importance of considering polysubstance use: lessons from cocaine research","volume":"192","author":"Liu","year":"2018","journal-title":"Drug Alcohol Depend"},{"key":"2026042910265709100_ref2","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1037\/adb0000464","article-title":"Types of cannabis and tobacco\/nicotine co-use and associated outcomes in young adulthood","volume":"33","author":"Tucker","year":"2019","journal-title":"Psychol Addict Behav"},{"key":"2026042910265709100_ref3","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1080\/00952990.2016.1209513","article-title":"Interactions between nicotine and drugs of abuse: a review of preclinical findings","volume":"43","author":"Kohut","year":"2017","journal-title":"Am J Drug Alcohol Abuse"},{"key":"2026042910265709100_ref4","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1111\/j.1360-0443.2012.03843.x","article-title":"Clinical correlates of co-occurring cannabis and tobacco use: a systematic review","volume":"107","author":"Peters","year":"2012","journal-title":"Addiction."},{"key":"2026042910265709100_ref5","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.drugalcdep.2013.10.003","article-title":"Psychiatric, psychosocial, and physical health correlates of co-occurring cannabis use disorders and nicotine dependence","volume":"134","author":"Peters","year":"2014","journal-title":"Drug Alcohol Depend"},{"key":"2026042910265709100_ref6","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.drugalcdep.2018.03.010","article-title":"The relation between gray matter volume and the use of alcohol, tobacco, cocaine and cannabis in male polysubstance users","volume":"187","author":"Kaag","year":"2018","journal-title":"Drug Alcohol Depend"},{"key":"2026042910265709100_ref7","doi-asserted-by":"publisher","first-page":"106109","DOI":"10.1016\/J.ADDBEH.2019.106109","article-title":"Patterns of cigarette, e-cigarette, and cannabis use among adult smokers in primary care 2014\u20132015","volume":"100","author":"Thrul","year":"2020","journal-title":"Addict Behav"},{"key":"2026042910265709100_ref8","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1111\/ajad.12186","article-title":"A review of co-morbid tobacco and cannabis use disorders: possible mechanisms to explain high rates of co-use","volume":"24","author":"Rabin","year":"2015","journal-title":"Am J Addict"},{"key":"2026042910265709100_ref9","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1080\/10826084.2018.1512623","article-title":"The relationship between tobacco and cannabis use: a review","volume":"54","author":"Lemyre","journal-title":"Subst Use Misuse"},{"key":"2026042910265709100_ref10","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1093\/ntr\/ntac267","article-title":"Nicotine enhances intravenous self-administration of cannabinoids in adult rats","volume":"25","author":"Stringfield","year":"2023","journal-title":"Nicotine Tob Res."},{"key":"2026042910265709100_ref11","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1007\/s00213-007-0863-3","article-title":"Reinforcement enhancing effect of nicotine and its attenuation by nicotinic antagonists in rats","volume":"194","author":"Liu","year":"2007","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref12","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1007\/s00213-003-1473-3","article-title":"Operant responding for a visual reinforcer in rats is enhanced by noncontingent nicotine: implications for nicotine self-administration and reinforcement","volume":"169","author":"Donny","year":"2003","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref13","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1038\/sj.npp.1301228","article-title":"The role of nicotinic acetylcholine receptors in the primary reinforcing and reinforcement-enhancing effects of nicotine","volume":"32","author":"Palmatier","year":"2007","journal-title":"Neuropsychopharmacology."},{"key":"2026042910265709100_ref14","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1007\/S00213-022-06266-7","article-title":"Elucidating the reinforcing effects of nicotine: a tribute to Nadia Chaudhri","volume":"240","author":"Sved","year":"2023","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref15","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1097\/FBP.0000000000000404","article-title":"A behavioral economic analysis of the value-enhancing effects of nicotine and varenicline and the role of nicotinic acetylcholine receptors in male and female rats","volume":"29","author":"Barrett","year":"2018","journal-title":"Behav Pharmacol"},{"key":"2026042910265709100_ref16","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/S00213-012-2832-8","article-title":"Nicotine-induced enhancement of responding for conditioned reinforcement in rats: role of prior nicotine exposure and \u03b14\u03b22 nicotinic receptors","volume":"225","author":"Guy","year":"2013","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref17","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/J.NEUROPHARM.2018.12.011","article-title":"Nicotine enhances responding for conditioned reinforcement via \u03b14\u03b22 nicotinic acetylcholine receptors in the ventral tegmental area, but not the nucleus accumbens or the prefrontal cortex","volume":"148","author":"Tabbara","year":"2019","journal-title":"Neuropharmacology."},{"key":"2026042910265709100_ref18","doi-asserted-by":"publisher","first-page":"3563","DOI":"10.1007\/S12035-018-1319-Y","article-title":"Astrocytic mechanisms involving kynurenic acid control \u03949-tetrahydrocannabinol-induced increases in glutamate release in brain reward-processing areas","volume":"56","author":"Secci","year":"2019","journal-title":"Mol Neurobiol"},{"key":"2026042910265709100_ref19","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1038\/nn.3540","article-title":"Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid","volume":"16","author":"Justinova","year":"2013","journal-title":"Nat Neurosci"},{"key":"2026042910265709100_ref20","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00213-020-05684-9","article-title":"Intravenous self-administration of delta-9-THC in adolescent rats produces long-lasting alterations in behavior and receptor protein expression","volume":"238","author":"Stringfield","year":"2020","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref21","doi-asserted-by":"publisher","first-page":"23990","DOI":"10.1038\/S41598-021-03242-7","article-title":"Pharmacokinetics and central accumulation of delta-9-tetrahydrocannabinol (THC) and its bioactive metabolites are influenced by route of administration and sex in rats","volume":"11","author":"Baglot","year":"2021","journal-title":"Sci Rep"},{"key":"2026042910265709100_ref22","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1038\/NPP.2017.21","article-title":"Attenuating nicotine reinforcement and relapse by enhancing endogenous brain levels of kynurenic acid in rats and squirrel monkeys","volume":"42","author":"Secci","year":"2017","journal-title":"Neuropsychopharmacology."},{"key":"2026042910265709100_ref23","doi-asserted-by":"publisher","first-page":"108718","DOI":"10.1016\/J.DRUGALCDEP.2021.108718","article-title":"Investigating sex differences in acute intoxication and verbal memory errors after ad libitum cannabis concentrate use","volume":"223","author":"Gibson","year":"2021","journal-title":"Drug Alcohol Depend"},{"key":"2026042910265709100_ref24","doi-asserted-by":"publisher","first-page":"e0313091","DOI":"10.1371\/journal.pone.0313091","article-title":"Fatty acid binding protein 7 plays an important modulatory sex-dependent role on brain endocannabinoid levels and THC metabolism","volume":"19","author":"Penman","year":"2024","journal-title":"PLoS One"},{"key":"2026042910265709100_ref25","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1007\/S00213-005-0178-1","article-title":"Complex interactions between nicotine and nonpharmacological stimuli reveal multiple roles for nicotine in reinforcement","volume":"184","author":"Chaudhri","year":"2006","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref26","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.drugalcdep.2006.11.020","article-title":"The reinforcement enhancing effects of nicotine depend on the incentive value of non-drug reinforcers and increase with repeated drug injections","volume":"89","author":"Palmatier","year":"2007","journal-title":"Drug Alcohol Depend"},{"key":"2026042910265709100_ref27","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s00213-005-0183-4","article-title":"Dissociating the primary reinforcing and reinforcement-enhancing effects of nicotine using a rat self-administration paradigm with concurrently available drug and environmental reinforcers","volume":"184","author":"Palmatier","year":"2006","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref28","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00213-006-0522-0","article-title":"Operant responding for conditioned and unconditioned reinforcers in rats is differentially enhanced by the primary reinforcing and reinforcement-enhancing effects of nicotine","volume":"189","author":"Chaudhri","year":"2006","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref29","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/J.PBB.2014.06.013","article-title":"Nicotine enhances the expression of a sucrose or cocaine conditioned place preference in adult male rats","volume":"124","author":"Buffalari","year":"2014","journal-title":"Pharmacol Biochem Behav"},{"key":"2026042910265709100_ref30","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1007\/S00213-002-1079-1","article-title":"Enhancement of cocaine-seeking behavior by repeated nicotine exposure in rats","volume":"162","author":"Bechtholt","year":"2002","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref31","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1007\/s00213-002-1330-9","article-title":"Nicotine increases alcohol self-administration and reinstates alcohol seeking in rats","volume":"168","author":"L\u00ea","year":"2003","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref32","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1007\/S00213-020-05669-8","article-title":"Chronic nicotine increases alcohol self-administration in adult male Wistar rats","volume":"238","author":"Montanari","year":"2021","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref33","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1093\/ntr\/ntz056","article-title":"Sex differences in the reward-enhancing effects of nicotine on ethanol reinforcement: a reinforcer demand analysis","volume":"22","author":"Barrett","year":"2020","journal-title":"Nicotine Tob Res"},{"key":"2026042910265709100_ref34","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.1007\/s00213-019-5174-y","article-title":"Therapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats","volume":"236","author":"Waeiss","year":"2019","journal-title":"Psychopharmacology"},{"key":"2026042910265709100_ref35","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1016\/S0022-3565(24)39179-7","article-title":"Evidence that nicotinic \u03b17 receptors are not involved in the hyperlocomotor and rewarding effects of nicotine","volume":"294","author":"Grottick","year":"2000","journal-title":"J Pharmacol Exp Ther"},{"key":"2026042910265709100_ref36","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1080\/14622200110073380","article-title":"The nicotinic antagonist methyllycaconitine has differential effects on nicotine self-administration and nicotine withdrawal in the rat","volume":"3","author":"Markou","year":"2001","journal-title":"Nicotine Tob Res"},{"key":"2026042910265709100_ref37","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/J.TIPS.2023.05.003","article-title":"Targeting corticostriatal transmission for the treatment of cannabinoid use disorder","volume":"44","author":"Ferr\u00e9","year":"2023","journal-title":"Trends Pharmacol Sci"},{"key":"2026042910265709100_ref38","doi-asserted-by":"publisher","first-page":"PL185","DOI":"10.1016\/S0024-3205(97)00665-6","article-title":"Sex difference in up-regulation of nicotine acetylcholine receptors in rat brain","volume":"61","author":"Koylu","year":"1997","journal-title":"Life Sci"},{"key":"2026042910265709100_ref39","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/nn.4313","article-title":"Opposing mechanisms mediate morphine- and cocaine-induced generation of silent synapses","volume":"19","author":"Graziane","year":"2016","journal-title":"Nat Neurosci"},{"key":"2026042910265709100_ref40","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1038\/s41386-019-0452-2","article-title":"Sequential cocaine-alcohol self-administration produces adaptations in rat nucleus accumbens core glutamate homeostasis that are distinct from those produced by cocaine self-administration alone","volume":"45","author":"Stennett","year":"2019","journal-title":"Neuropsychopharmacology."}],"container-title":["International Journal of Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ijnp\/advance-article-pdf\/doi\/10.1093\/ijnp\/pyag015\/67715550\/pyag015.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ijnp\/article-pdf\/29\/4\/pyag015\/67715550\/pyag015.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ijnp\/article-pdf\/29\/4\/pyag015\/67715550\/pyag015.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T14:27:15Z","timestamp":1777472835000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ijnp\/article\/doi\/10.1093\/ijnp\/pyag015\/8571422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4,6]]}},"URL":"https:\/\/doi.org\/10.1093\/ijnp\/pyag015","relation":{},"ISSN":["1461-1457","1469-5111"],"issn-type":[{"value":"1461-1457","type":"print"},{"value":"1469-5111","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,4,1]]},"article-number":"pyag015"}}