{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:43:24Z","timestamp":1784097804647,"version":"3.55.0"},"reference-count":92,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,6]],"date-time":"2021-06-06T00:00:00Z","timestamp":1622937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA 045140"],"award-info":[{"award-number":["DA 045140"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA050118"],"award-info":[{"award-number":["DA050118"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DA049212"],"award-info":[{"award-number":["DA049212"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The intravenous cocaine self-administration model is widely used to characterize the neurobiology of cocaine seeking. When studies are aimed at understanding relapse to cocaine-seeking, a post-cocaine abstinence period is imposed, followed by \u201crelapse\u201d tests to assess the ability of drug-related stimuli (\u201cprimes\u201d) to evoke the resumption of the instrumental response previously made to obtain cocaine. Here, we review the literature on the impact of post-cocaine abstinence procedures on neurobiology, finding that the prelimbic and infralimbic regions of the prefrontal cortex are recruited by extinction training, and are not part of the relapse circuitry when extinction training does not occur. Pairing cocaine infusions with discrete cues recruits the involvement of the NA, which together with the dorsal striatum, is a key part of the relapse circuit regardless of abstinence procedures. Differences in molecular adaptations in the NA core include increased expression of GluN1 and glutamate receptor signaling partners after extinction training. AMPA receptors and glutamate transporters are similarly affected by abstinence and extinction. Glutamate receptor antagonists show efficacy at reducing relapse following extinction and abstinence, with a modest increase in efficacy of compounds that restore glutamate homeostasis after extinction training. Imaging studies in humans reveal cocaine-induced adaptations that are similar to those produced after extinction training. Thus, while instrumental extinction training does not have face validity, its use does not produce adaptations distinct from human cocaine users.<\/jats:p>","DOI":"10.3390\/ijms22116113","type":"journal-article","created":{"date-parts":[[2021,6,6]],"date-time":"2021-06-06T23:59:55Z","timestamp":1623023995000},"page":"6113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Extinction vs. Abstinence: A Review of the Molecular and Circuit Consequences of Different Post-Cocaine Experiences"],"prefix":"10.3390","volume":"22","author":[{"given":"Marek","family":"Schwendt","sequence":"first","affiliation":[{"name":"Psychology Department, University of Florida, Gainesville, FL 32611, USA"},{"name":"Center for Addiction Research and Education, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori A.","family":"Knackstedt","sequence":"additional","affiliation":[{"name":"Psychology Department, University of Florida, Gainesville, FL 32611, USA"},{"name":"Center for Addiction Research and Education, University of Florida, Gainesville, FL 32611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1038\/npp.2016.287","article-title":"Incubation of methamphetamine but not heroin craving after voluntary abstinence in male and female rats","volume":"42","author":"Venniro","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.tins.2011.06.001","article-title":"Neurobiology of the incubation of drug craving","volume":"34","author":"Pickens","year":"2011","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2663","DOI":"10.1111\/ejn.14418","article-title":"Incentive and dopamine sensitization produced by intermittent but not long access cocaine self-administration","volume":"50","author":"Kawa","year":"2019","journal-title":"Eur. 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