{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:19:24Z","timestamp":1768522764983,"version":"3.49.0"},"posted":{"date-parts":[[2025,7,19]]},"group-title":"Neuroscience","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"BS","award":["NIH DA036534"],"award-info":[{"award-number":["NIH DA036534"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,7,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Chronic substance use is associated with alterations in multiple forms of cost-benefit decision making, which may prolong and exacerbate continued use. Cues that predict reward can cause substantial shifts in a variety of reward-directed behavior, including decision making. In contrast, how decision making is modulated by cues predictive of punishment is much less well understood. To begin to address these issues, male and female Long-Evans rats were tested in a novel decision-making task in which they chose between a small, \u201csafe\u201d reward and a large reward that was punished by a mild footshock when it was preceded by a probabilistically delivered cue prior to the choice. Rats of both sexes were sensitive to the cue, preferring the large reward in the absence of the cue but the small reward in the presence of the cue. Acute systemic amphetamine reduced choice of the large reward and diminished the efficacy of the cue in guiding choice behavior. Chronic cocaine led to divergent patterns of cue insensitivity in males and females; males increased choice of the large reward on cued trials, whereas females increased avoidance of the large reward on uncued trials. Similar to acute amphetamine, acute systemic administration of the D2\/3 dopamine receptor agonist bromocriptine reduced preference for the large reward across all groups. These findings highlight the contributions of punishment cues to decision making, as well as the importance of sex as a biological variable in investigating cognitive alterations caused by chronic substance use.<\/jats:p>","DOI":"10.1101\/2025.07.15.664953","type":"posted-content","created":{"date-parts":[[2025,7,20]],"date-time":"2025-07-20T04:30:15Z","timestamp":1752985815000},"source":"Crossref","is-referenced-by-count":0,"title":["A novel cost-benefit decision-making task involving cued punishment; effects of sex and psychostimulant administration"],"prefix":"10.64898","author":[{"given":"Mojdeh","family":"Faraji","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Bizon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Setlow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"2","key":"2025072219300618000_2025.07.15.664953v1.1","first-page":"e22090","article-title":"Trends of Cocaine Use and Manifestations in Hospitalized Patients: A Cross- Sectional Study","volume":"14","year":"2022","journal-title":"Cureus"},{"key":"2025072219300618000_2025.07.15.664953v1.2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1360-0443.2001.961736.x"},{"key":"2025072219300618000_2025.07.15.664953v1.3","doi-asserted-by":"publisher","DOI":"10.1007\/PL00005488"},{"key":"2025072219300618000_2025.07.15.664953v1.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5426-10.2011"},{"issue":"4","key":"2025072219300618000_2025.07.15.664953v1.5","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S0893-133X(98)00091-8","article-title":"Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan- depleted normal volunteers: evidence for monoaminergic mechanisms","volume":"20","year":"1999","journal-title":"Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology"},{"key":"2025072219300618000_2025.07.15.664953v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2005.09.005"},{"key":"2025072219300618000_2025.07.15.664953v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3014"},{"key":"2025072219300618000_2025.07.15.664953v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-008-1173-0"},{"key":"2025072219300618000_2025.07.15.664953v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0376-8716(01)00197-1"},{"key":"2025072219300618000_2025.07.15.664953v1.10","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2003.00669.x"},{"key":"2025072219300618000_2025.07.15.664953v1.11","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2485-z"},{"key":"2025072219300618000_2025.07.15.664953v1.12","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.11030489"},{"key":"2025072219300618000_2025.07.15.664953v1.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2004.08.013"},{"key":"2025072219300618000_2025.07.15.664953v1.14","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-020-05506-y"},{"key":"2025072219300618000_2025.07.15.664953v1.15","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2013.00149"},{"key":"2025072219300618000_2025.07.15.664953v1.16","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291713001839"},{"key":"2025072219300618000_2025.07.15.664953v1.17","doi-asserted-by":"publisher","DOI":"10.1037\/1064-1297.13.4.311"},{"key":"2025072219300618000_2025.07.15.664953v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.addbeh.2014.02.015"},{"key":"2025072219300618000_2025.07.15.664953v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3932(00)00136-6"},{"key":"2025072219300618000_2025.07.15.664953v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2007.02.004"},{"key":"2025072219300618000_2025.07.15.664953v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.48"},{"key":"2025072219300618000_2025.07.15.664953v1.22","doi-asserted-by":"crossref","unstructured":"Orsini, C.A. , et al., Recent Updates in Modeling Risky Decision Making in Rodents , in Psychiatric Disorders: Methods and Protocols, F.H. Kobeissy , Editor. 2019, Springer New York: New York, NY. p. 79\u201392.","DOI":"10.1007\/978-1-4939-9554-7_5"},{"key":"2025072219300618000_2025.07.15.664953v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.295"},{"key":"2025072219300618000_2025.07.15.664953v1.24","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000509"},{"key":"2025072219300618000_2025.07.15.664953v1.25","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.pbb.2017.07.013","article-title":"Age and impulsive behavior in drug addiction: A review of past research and future directions","volume":"164","year":"2018","journal-title":"Pharmacol Biochem Behav"},{"issue":"6","key":"2025072219300618000_2025.07.15.664953v1.26","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/bsl.845","article-title":"Executive dysfunction as a risk marker for substance abuse: The role of impulsive personality traits","volume":"26","year":"2008","journal-title":"Behavioral Sciences & the Law"},{"key":"2025072219300618000_2025.07.15.664953v1.27","doi-asserted-by":"crossref","first-page":"692266","DOI":"10.3389\/fpsyt.2021.692266","article-title":"Altered Neural Processing of Reward and Punishment in Women With Methamphetamine Use Disorder","volume":"12","year":"2021","journal-title":"Front Psychiatry"},{"key":"2025072219300618000_2025.07.15.664953v1.28","doi-asserted-by":"crossref","first-page":"320","DOI":"10.3389\/fpsyt.2020.00320","article-title":"Smaller Feedback-Related Negativity (FRN) Reflects the Risky Decision-Making Deficits of Methamphetamine Dependent Individuals","volume":"11","year":"2020","journal-title":"Front Psychiatry"},{"key":"2025072219300618000_2025.07.15.664953v1.29","doi-asserted-by":"publisher","DOI":"10.1126\/science.1098975"},{"key":"2025072219300618000_2025.07.15.664953v1.30","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fnbeh.2018.00108","article-title":"Repeated Cocaine Exposure Attenuates the Desire to Actively Avoid: A Novel Active Avoidance Runway Task","volume":"12","year":"2018","journal-title":"Front Behav Neurosci"},{"key":"2025072219300618000_2025.07.15.664953v1.31","doi-asserted-by":"crossref","first-page":"107961","DOI":"10.1016\/j.nlm.2024.107961","article-title":"Random interval schedule of reinforcement influences punishment resistance for cocaine in rats","volume":"213","year":"2024","journal-title":"Neurobiology of Learning and Memory"},{"issue":"9","key":"2025072219300618000_2025.07.15.664953v1.32","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.euroneuro.2008.04.005","article-title":"Certain or uncertain cocaine expectations influence accumbens dopamine responses to \u2018self-administered cocaine and non-rewarded operant behavior","volume":"18","year":"2008","journal-title":"European Neuropsychopharmacology"},{"key":"2025072219300618000_2025.07.15.664953v1.33","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0000000000000448"},{"key":"2025072219300618000_2025.07.15.664953v1.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3772-11.2011"},{"key":"2025072219300618000_2025.07.15.664953v1.35","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000111"},{"key":"2025072219300618000_2025.07.15.664953v1.36","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-011-2363-8"},{"key":"2025072219300618000_2025.07.15.664953v1.37","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.121.3.543"},{"key":"2025072219300618000_2025.07.15.664953v1.38","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-4006-y"},{"key":"2025072219300618000_2025.07.15.664953v1.39","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2777-14.2015"},{"issue":"11","key":"2025072219300618000_2025.07.15.664953v1.40","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1093\/ijnp\/pyab041","article-title":"Impaired Learning From Negative Feedback in Stimulant Use Disorder: Dopaminergic Modulation","volume":"24","year":"2021","journal-title":"Int J Neuropsychopharmacol"},{"key":"2025072219300618000_2025.07.15.664953v1.41","doi-asserted-by":"crossref","first-page":"109791","DOI":"10.1016\/j.pnpbp.2019.109791","article-title":"Distinct relationships between risky decision making and cocaine self- administration under short- and long-access conditions","volume":"98","year":"2020","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2025072219300618000_2025.07.15.664953v1.42","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.neuropharm.2018.07.018","article-title":"Contributions of medial prefrontal cortex to decision making involving risk of punishment","volume":"139","year":"2018","journal-title":"Neuropharmacology"},{"key":"2025072219300618000_2025.07.15.664953v1.43","doi-asserted-by":"crossref","unstructured":"Hashemnia, S. , D.R. Euston , and A.J. Gruber , Amphetamine reduces reward encoding and stabilizes neural dynamics in rat anterior cingulate cortex. Elife, 2020. 9.","DOI":"10.7554\/eLife.56755"},{"key":"2025072219300618000_2025.07.15.664953v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.121"},{"key":"2025072219300618000_2025.07.15.664953v1.45","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050174"},{"issue":"3","key":"2025072219300618000_2025.07.15.664953v1.46","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.biopsych.2023.08.021","article-title":"Win-Paired Cues Modulate the Effect of Dopamine Neuron Sensitization on Decision Making and Cocaine Self-administration: Divergent Effects Across Sex","volume":"95","year":"2024","journal-title":"Biol Psychiatry"},{"key":"2025072219300618000_2025.07.15.664953v1.47","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.10.002"},{"key":"2025072219300618000_2025.07.15.664953v1.48","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-024-01925-z"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.07.15.664953","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:09:46Z","timestamp":1768468186000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.07.15.664953"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,19]]},"references-count":48,"URL":"https:\/\/doi.org\/10.1101\/2025.07.15.664953","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.bbr.2025.115781","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,7,19]]},"subtype":"preprint"}}