{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T11:02:52Z","timestamp":1784890972878,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,21]]},"group-title":"Neuroscience","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"crossref","award":["DA046411"],"award-info":[{"award-number":["DA046411"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Cigarette smoking remains one of the most important preventable causes of premature death worldwide. However, the mechanisms sustaining nicotine dependence and relapse are incompletely understood, particularly the role of impulsive action in persistent tobacco use. Dopamine D1 and nicotinic acetylcholine receptors both regulate nicotine-related behavior, but whether they contribute differently to nicotine-motivated responding and nicotine-induced impulsive action is unclear. The present study examined the effects of D1 receptor blockade and stimulation in male and female rats trained to self-administer nicotine intravenously in a Go\/No- Go task. Nicotine was available during Go periods but not during No-Go periods, and impulsive action was measured as the percentage of active lever responses during No-Go periods. The D1 receptor antagonist SCH23390 reduced nicotine intake and active lever responding during Go periods and affected the percentage of active lever responses during No-Go periods. However, SCH23390 also reduced inactive lever responding, so its effect on impulsive action could not be separated from a general reduction in operant output. In contrast, the D1 receptor agonist A77636 reduced nicotine intake and Go-period responding without affecting No-Go responding, indicating that D1 receptor stimulation reduced nicotine-motivated responding without altering impulsive action. Rats showed greater No-Go responding during nicotine self-administration than during saline self-administration, indicating that nicotine increased impulsive action rather than general operant responding. The non-selective nicotinic antagonist mecamylamine reduced nicotine-motivated responding and decreased No-Go responding, indicating reduced impulsive action. These findings suggest that nicotinic acetylcholine receptor signaling plays a major role in nicotine-induced impulsive action, whereas D1 receptor signaling contributes more clearly to nicotine-motivated responding. D1 receptor agonism may reduce nicotine-motivated behavior without affecting nicotine-induced impulsive action.<\/jats:p>","DOI":"10.64898\/2026.07.16.739006","type":"posted-content","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:36:26Z","timestamp":1784694986000},"source":"Crossref","is-referenced-by-count":0,"title":["Dissociable roles of dopamine D1 and nicotinic receptors in nicotine-motivated responding and impulsive action in a Go\/No-Go self-administration task"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2793-022X","authenticated-orcid":false,"given":"Ranjithkumar","family":"Chellian","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Florida, Gainesville, FL, USA"},{"name":"Department of Biomedical Sciences, Texas A&M University, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Huisman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Caglayan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-1970","authenticated-orcid":false,"given":"Adriaan W.","family":"Bruijnzeel","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026072403401870000_2026.07.16.739006v1.1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.pbb.2018.10.006","article-title":"Cholinergic and dopaminergic interactions alter attention and response inhibition in Long-Evans rats performing the 5-choice serial reaction time task","volume":"175","year":"2018","journal-title":"Pharmacology, biochemistry, and behavior"},{"key":"2026072403401870000_2026.07.16.739006v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2013.06.005"},{"key":"2026072403401870000_2026.07.16.739006v1.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0809890"},{"key":"2026072403401870000_2026.07.16.739006v1.4","doi-asserted-by":"publisher","DOI":"10.1007\/s002130000378"},{"key":"2026072403401870000_2026.07.16.739006v1.5","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1177\/02698811241230255","article-title":"Mifepristone decreases nicotine intake in dependent and non-dependent adult rats","volume":"38","year":"2024","journal-title":"J Psychopharmacol"},{"key":"2026072403401870000_2026.07.16.739006v1.6","doi-asserted-by":"crossref","first-page":"1415219","DOI":"10.3389\/fphar.2024.1415219","article-title":"Sex differences in nicotine intake and relapse behavior in nicotine-dependent adult wistar rats","volume":"15","year":"2024","journal-title":"Front Pharmacol"},{"key":"2026072403401870000_2026.07.16.739006v1.7","first-page":"1","article-title":"Dopamine D1-like receptor blockade and stimulation decreases operant responding for nicotine and food in male and female rats","volume":"12","year":"2022","journal-title":"Scientific Reports"},{"key":"2026072403401870000_2026.07.16.739006v1.8","doi-asserted-by":"crossref","first-page":"e13312","DOI":"10.1111\/adb.13312","article-title":"Dopamine D1-like receptor activation decreases nicotine intake in rats with short or long access to nicotine","volume":"28","year":"2023","journal-title":"Addiction biology"},{"key":"2026072403401870000_2026.07.16.739006v1.9","doi-asserted-by":"crossref","unstructured":"Chellian R , Behnood-Rod A , Wilson R , Lin K , Wing-Yan King G , Bruijnzeel AW (2023b) The D1\/D2-like receptor antagonist flupentixol and the D2-like receptor antagonist L-741626 decrease operant responding for nicotine and food and locomotor activity in male and female rats. Journal of Psychopharmacology: 02698811221147141.","DOI":"10.1177\/02698811221147141"},{"key":"2026072403401870000_2026.07.16.739006v1.10","doi-asserted-by":"crossref","unstructured":"Chellian R , Huisman G , Bruijnzeel AW (2026) Nicotine self-administration increases impulsive action: differential effects of nAChR modulators in a Go\/No-Go task. bioRxiv.","DOI":"10.64898\/2026.03.31.715632"},{"key":"2026072403401870000_2026.07.16.739006v1.11","doi-asserted-by":"publisher","DOI":"10.1007\/BF02244174"},{"key":"2026072403401870000_2026.07.16.739006v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(94)90353-0"},{"key":"2026072403401870000_2026.07.16.739006v1.13","doi-asserted-by":"publisher","DOI":"10.1007\/BF02245149"},{"key":"2026072403401870000_2026.07.16.739006v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.01.020"},{"key":"2026072403401870000_2026.07.16.739006v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.07.011"},{"key":"2026072403401870000_2026.07.16.739006v1.16","doi-asserted-by":"publisher","DOI":"10.1007\/s002130000497"},{"key":"2026072403401870000_2026.07.16.739006v1.17","doi-asserted-by":"publisher","DOI":"10.1136\/tobaccocontrol-2016-053305"},{"key":"2026072403401870000_2026.07.16.739006v1.18","doi-asserted-by":"publisher","DOI":"10.1037\/per0000099"},{"key":"2026072403401870000_2026.07.16.739006v1.19","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1021\/ml500094c","article-title":"Synthesis and Pharmacological Evaluation of DH\u03b2E Analogues as Neuronal Nicotinic Acetylcholine Receptor Antagonists","volume":"5","year":"2014","journal-title":"ACS Med Chem Lett"},{"key":"2026072403401870000_2026.07.16.739006v1.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2296-2"},{"key":"2026072403401870000_2026.07.16.739006v1.21","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00213-011-2558-z","article-title":"Effects of chronic nicotine, nicotine withdrawal and subsequent nicotine challenges on behavioural inhibition in rats","volume":"219","year":"2012","journal-title":"Psychopharmacology (Berl"},{"key":"2026072403401870000_2026.07.16.739006v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.110"},{"key":"2026072403401870000_2026.07.16.739006v1.23","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-005-0134-0"},{"key":"2026072403401870000_2026.07.16.739006v1.24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018898"},{"key":"2026072403401870000_2026.07.16.739006v1.25","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.neuropharm.2016.02.023","article-title":"Varenicline impairs extinction and enhances reinstatement across repeated cycles of nicotine self-administration in rats","volume":"105","year":"2016","journal-title":"Neuropharmacology"},{"key":"2026072403401870000_2026.07.16.739006v1.26","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1111\/add.70003","article-title":"Deficits in general and smoking-specific response inhibition in the Go\/No-Go task in individuals who smoke: A cross-sectional analysis","volume":"120","year":"2025","journal-title":"Addiction"},{"key":"2026072403401870000_2026.07.16.739006v1.27","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890160105"},{"key":"2026072403401870000_2026.07.16.739006v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.03.010"},{"key":"2026072403401870000_2026.07.16.739006v1.29","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1173-0"},{"key":"2026072403401870000_2026.07.16.739006v1.30","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a039610"},{"key":"2026072403401870000_2026.07.16.739006v1.31","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2011.11.009"},{"key":"2026072403401870000_2026.07.16.739006v1.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2004.05.006"},{"key":"2026072403401870000_2026.07.16.739006v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301454"},{"key":"2026072403401870000_2026.07.16.739006v1.34","doi-asserted-by":"publisher","DOI":"10.1007\/s10508-017-1010-9"},{"key":"2026072403401870000_2026.07.16.739006v1.35","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1607-3"},{"key":"2026072403401870000_2026.07.16.739006v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2007.11.003"},{"key":"2026072403401870000_2026.07.16.739006v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nn1846"},{"key":"2026072403401870000_2026.07.16.739006v1.38","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.28695"},{"key":"2026072403401870000_2026.07.16.739006v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2013.10.033"},{"key":"2026072403401870000_2026.07.16.739006v1.40","unstructured":"WHO (2025a) Tobacco. Available at: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/tobacco [Accessed June 25, 2026]."},{"key":"2026072403401870000_2026.07.16.739006v1.41","unstructured":"WHO (2025b) WHO report on the global tobacco epidemic, 2025: warning about the dangers of tobacco. World Health Organization."},{"key":"2026072403401870000_2026.07.16.739006v1.42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01323.x"},{"key":"2026072403401870000_2026.07.16.739006v1.43","first-page":"172","article-title":"Rewarding Effects of Nicotine in Adolescent and Adult Male and Female Rats as Measured Using Intracranial Self-stimulation","volume":"22","year":"2018","journal-title":"Nicotine & Tobacco Research"},{"key":"2026072403401870000_2026.07.16.739006v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2010.02.018"},{"key":"2026072403401870000_2026.07.16.739006v1.45","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-21-08528.1997"},{"key":"2026072403401870000_2026.07.16.739006v1.46","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.286"},{"key":"2026072403401870000_2026.07.16.739006v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108604"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.07.16.739006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:40:28Z","timestamp":1784889628000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.07.16.739006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":47,"URL":"https:\/\/doi.org\/10.64898\/2026.07.16.739006","relation":{},"subject":[],"published":{"date-parts":[[2026,7,21]]},"subtype":"preprint"}}