{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:48:31Z","timestamp":1768506511260,"version":"3.49.0"},"posted":{"date-parts":[[2023,6,9]]},"group-title":"Neuroscience","reference-count":91,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Addiction is characterized by continued drug use despite negative consequences. In an animal model, a subset of rats continues to self-administer cocaine despite footshock consequences, showing punishment resistance. We sought to test the hypothesis that punishment resistance arises from failure to exert goal-directed control over habitual cocaine seeking. While habits are not inherently permanent or maladaptive, continued use of habits under conditions that should encourage goal-directed control makes them maladaptive and inflexible. We trained male and female Sprague Dawley rats on a seeking-taking chained schedule of cocaine self-administration (2 h\/day). We then exposed them to 4 days of punishment testing, in which footshock (0.4 mA, 0.3 s) was delivered randomly on one-third of trials, immediately following completion of seeking and prior to extension of the taking lever. Before and after punishment testing (4 days pre-punishment and \u22654 days post-punishment), we assessed whether cocaine seeking was goal-directed or habitual using outcome devaluation via cocaine satiety. We found that punishment resistance was associated with continued use of habits, whereas punishment sensitivity was associated with increased goal-directed control. Although punishment resistance was not predicted by habitual responding pre-punishment, it was associated with habitual responding post-punishment. In parallel studies of food self-administration, we similarly observed that punishment resistance was associated with habitual responding post-punishment but not pre-punishment. These findings indicate that punishment resistance is related to habits that have become inflexible and persist under conditions that should encourage a transition to goal-directed behavior.<\/jats:p>","DOI":"10.1101\/2023.06.08.544242","type":"posted-content","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T22:20:10Z","timestamp":1686349210000},"source":"Crossref","is-referenced-by-count":1,"title":["Punishment resistance for cocaine is associated with inflexible habits in rats"],"prefix":"10.64898","author":[{"given":"Bradley O.","family":"Jones","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan S.","family":"Paladino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelis M.","family":"Cruz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haley F.","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Payton L.","family":"Kahanek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren N.","family":"Scarborough","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra F.","family":"Georges","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel J.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023061312200888000_2023.06.08.544242v1.1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1080\/14640748208400878","article-title":"Variations in the sensitivity of instrumental responding to reinforcer devaluation","volume":"34","year":"1982","journal-title":"The Quarterly Journal of Experimental Psychology Section B"},{"key":"2023061312200888000_2023.06.08.544242v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1399"},{"key":"2023061312200888000_2023.06.08.544242v1.3","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12609"},{"key":"2023061312200888000_2023.06.08.544242v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2008.04.005"},{"key":"2023061312200888000_2023.06.08.544242v1.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3630-06.2006"},{"key":"2023061312200888000_2023.06.08.544242v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(98)00033-1"},{"key":"2023061312200888000_2023.06.08.544242v1.7","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-02-00666.2003"},{"key":"2023061312200888000_2023.06.08.544242v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.131"},{"key":"2023061312200888000_2023.06.08.544242v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2013.01.025"},{"key":"2023061312200888000_2023.06.08.544242v1.10","doi-asserted-by":"publisher","DOI":"10.1126\/science.1158136"},{"key":"2023061312200888000_2023.06.08.544242v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2023.109490"},{"key":"2023061312200888000_2023.06.08.544242v1.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1406324111"},{"key":"2023061312200888000_2023.06.08.544242v1.13","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3758\/s13420-021-00488-z","article-title":"Context, attention, and the switch between habit and goal-direction in behavior","volume":"49","year":"2021","journal-title":"Learn Behav"},{"key":"2023061312200888000_2023.06.08.544242v1.14","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2020.107163"},{"key":"2023061312200888000_2023.06.08.544242v1.15","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1016\/j.neubiorev.2021.10.043","article-title":"New directions in modelling dysregulated reward seeking for food and drugs","volume":"132","year":"2022","journal-title":"Neurosci Biobehav Rev"},{"key":"2023061312200888000_2023.06.08.544242v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/nature12024"},{"key":"2023061312200888000_2023.06.08.544242v1.17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07153.x"},{"key":"2023061312200888000_2023.06.08.544242v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2012.02.024"},{"key":"2023061312200888000_2023.06.08.544242v1.19","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2014.00301"},{"key":"2023061312200888000_2023.06.08.544242v1.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-018-4937-1"},{"key":"2023061312200888000_2023.06.08.544242v1.21","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1007\/s00213-017-4808-1","article-title":"Different functional domains measured by cocaine selfadministration under the progressive-ratio and punishment schedules in male Wistar rats","volume":"235","year":"2018","journal-title":"Psychopharmacology"},{"key":"2023061312200888000_2023.06.08.544242v1.22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1099020"},{"key":"2023061312200888000_2023.06.08.544242v1.23","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1985.0010"},{"key":"2023061312200888000_2023.06.08.544242v1.24","doi-asserted-by":"publisher","DOI":"10.3758\/BF03199935"},{"key":"2023061312200888000_2023.06.08.544242v1.25","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41386-020-0618-y","article-title":"Let\u2019s agree to agree: a comment on Hogarth (2020), with a plea for not-so-competing theories of addiction","volume":"45","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"2023061312200888000_2023.06.08.544242v1.26","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12644"},{"key":"2023061312200888000_2023.06.08.544242v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/nn1579"},{"key":"2023061312200888000_2023.06.08.544242v1.28","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-psych-122414-033457"},{"key":"2023061312200888000_2023.06.08.544242v1.29","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1037\/adb0000518","article-title":"Recovery from addiction: Behavioral economics and value-based decision making","volume":"34","year":"2020","journal-title":"Psychol Addict Behav"},{"key":"2023061312200888000_2023.06.08.544242v1.30","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2615-18.2018"},{"key":"2023061312200888000_2023.06.08.544242v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.105"},{"key":"2023061312200888000_2023.06.08.544242v1.32","doi-asserted-by":"publisher","DOI":"10.1111\/adb.13041"},{"key":"2023061312200888000_2023.06.08.544242v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms3264"},{"key":"2023061312200888000_2023.06.08.544242v1.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-020-0600-8"},{"key":"2023061312200888000_2023.06.08.544242v1.35","doi-asserted-by":"publisher","DOI":"10.1037\/0097-7403.30.2.104"},{"key":"2023061312200888000_2023.06.08.544242v1.36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1819978116"},{"key":"2023061312200888000_2023.06.08.544242v1.37","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0310-20.2020"},{"key":"2023061312200888000_2023.06.08.544242v1.38","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14166"},{"key":"2023061312200888000_2023.06.08.544242v1.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2018.07.022"},{"key":"2023061312200888000_2023.06.08.544242v1.40","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0047-3"},{"key":"2023061312200888000_2023.06.08.544242v1.41","doi-asserted-by":"crossref","first-page":"e2221634120","DOI":"10.1073\/pnas.2221634120","article-title":"A cognitive pathway to punishment insensitivity","volume":"120","year":"2023","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023061312200888000_2023.06.08.544242v1.42","doi-asserted-by":"crossref","unstructured":"Jean-Richard-Dit-Bressel P , Ma C , Bradfield LA , Killcross S , McNally GP (2019). Punishment insensitivity emerges from impaired contingency detection, not aversion insensitivity or reward dominance. Elife 8: .","DOI":"10.7554\/eLife.52765"},{"key":"2023061312200888000_2023.06.08.544242v1.43","doi-asserted-by":"publisher","DOI":"10.1101\/lm.053621.122"},{"key":"2023061312200888000_2023.06.08.544242v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.6"},{"key":"2023061312200888000_2023.06.08.544242v1.45","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0348-12.2012"},{"key":"2023061312200888000_2023.06.08.544242v1.46","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187801"},{"key":"2023061312200888000_2023.06.08.544242v1.47","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2012.59"},{"key":"2023061312200888000_2023.06.08.544242v1.48","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-016-4393-8"},{"key":"2023061312200888000_2023.06.08.544242v1.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2016.06.021"},{"key":"2023061312200888000_2023.06.08.544242v1.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2014.10.045"},{"key":"2023061312200888000_2023.06.08.544242v1.51","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2014.06.037"},{"key":"2023061312200888000_2023.06.08.544242v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2014.02.002"},{"key":"2023061312200888000_2023.06.08.544242v1.53","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/s41583-020-0289-z","article-title":"The transition to compulsion in addiction","volume":"21","year":"2020","journal-title":"Nat Rev Neurosci"},{"key":"2023061312200888000_2023.06.08.544242v1.54","doi-asserted-by":"crossref","first-page":"397","DOI":"10.31887\/DCNS.2006.8.4\/smaier","article-title":"Behavioral control, the medial prefrontal cortex, and resilience","volume":"8","year":"2006","journal-title":"Dialogues Clin Neurosci"},{"key":"2023061312200888000_2023.06.08.544242v1.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.08.039"},{"key":"2023061312200888000_2023.06.08.544242v1.56","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.108.1.44"},{"key":"2023061312200888000_2023.06.08.544242v1.57","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4677-14.2015"},{"key":"2023061312200888000_2023.06.08.544242v1.58","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.104"},{"key":"2023061312200888000_2023.06.08.544242v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2013.09.011"},{"key":"2023061312200888000_2023.06.08.544242v1.60","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.115.2.394"},{"key":"2023061312200888000_2023.06.08.544242v1.61","doi-asserted-by":"publisher","DOI":"10.1007\/s002130000498"},{"key":"2023061312200888000_2023.06.08.544242v1.62","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000111"},{"key":"2023061312200888000_2023.06.08.544242v1.63","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1921-05.2005"},{"key":"2023061312200888000_2023.06.08.544242v1.64","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmod.2009.07.004"},{"key":"2023061312200888000_2023.06.08.544242v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0789-4"},{"key":"2023061312200888000_2023.06.08.544242v1.66","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-007-0805-0"},{"key":"2023061312200888000_2023.06.08.544242v1.67","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-014-3648-5"},{"key":"2023061312200888000_2023.06.08.544242v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2003.11.013"},{"key":"2023061312200888000_2023.06.08.544242v1.69","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5578-03.2004"},{"key":"2023061312200888000_2023.06.08.544242v1.70","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12342"},{"key":"2023061312200888000_2023.06.08.544242v1.71","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1007\/s00213-015-4033-8","article-title":"Cortical GluN2B deletion attenuates punished suppression of food reward-seeking","volume":"232","year":"2015","journal-title":"Psychopharmacology"},{"key":"2023061312200888000_2023.06.08.544242v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2010.12.038"},{"key":"2023061312200888000_2023.06.08.544242v1.73","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.cub.2022.01.055","article-title":"Dopamine signaling in the dorsomedial striatum promotes compulsive behavior","volume":"32","year":"2022","journal-title":"Curr Biol"},{"key":"2023061312200888000_2023.06.08.544242v1.74","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2458-17.2017"},{"key":"2023061312200888000_2023.06.08.544242v1.75","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2017.09.003"},{"key":"2023061312200888000_2023.06.08.544242v1.76","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06844.x"},{"key":"2023061312200888000_2023.06.08.544242v1.77","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1037\/xan0000247","article-title":"Context and renewal of habits and goal-directed actions after extinction","volume":"46","year":"2020","journal-title":"J Exp Psychol Anim Learn Cogn"},{"key":"2023061312200888000_2023.06.08.544242v1.78","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1037\/bne0000422","article-title":"Renewal of goal direction with a context change after habit learning","volume":"135","year":"2021","journal-title":"Behav Neurosci"},{"key":"2023061312200888000_2023.06.08.544242v1.79","doi-asserted-by":"publisher","DOI":"10.1037\/xan0000045"},{"key":"2023061312200888000_2023.06.08.544242v1.80","doi-asserted-by":"crossref","first-page":"107161","DOI":"10.1016\/j.nlm.2020.107161","article-title":"Some factors that restore goal-direction to a habitual behavior","volume":"169","year":"2020","journal-title":"Neurobiol Learn Mem"},{"key":"2023061312200888000_2023.06.08.544242v1.81","doi-asserted-by":"publisher","DOI":"10.1126\/science.1098975"},{"key":"2023061312200888000_2023.06.08.544242v1.82","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2814-18.2019"},{"key":"2023061312200888000_2023.06.08.544242v1.83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1213460109"},{"key":"2023061312200888000_2023.06.08.544242v1.84","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08000.x"},{"key":"2023061312200888000_2023.06.08.544242v1.85","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/adb.12594","article-title":"Chemogenetic inhibition of direct pathway striatal neurons normalizes pathological, cue-induced reinstatement of drug-seeking in rats","volume":"24","year":"2019","journal-title":"Addict Biol"},{"key":"2023061312200888000_2023.06.08.544242v1.86","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1919"},{"key":"2023061312200888000_2023.06.08.544242v1.87","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2004.03095.x"},{"key":"2023061312200888000_2023.06.08.544242v1.88","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2005.07.012"},{"key":"2023061312200888000_2023.06.08.544242v1.89","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04218.x"},{"key":"2023061312200888000_2023.06.08.544242v1.90","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4072-10.2010"},{"key":"2023061312200888000_2023.06.08.544242v1.91","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyz023"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.06.08.544242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T04:45:59Z","timestamp":1768452359000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.06.08.544242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,9]]},"references-count":91,"URL":"https:\/\/doi.org\/10.1101\/2023.06.08.544242","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.addicn.2024.100148","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,6,9]]},"subtype":"preprint"}}