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dc.contributor.authorFouyssac, Maxime
dc.contributor.authorPeña-Oliver, Yolanda
dc.contributor.authorPuaud, Mickaёl
dc.contributor.authorLim, Nicole TY
dc.contributor.authorGiuliano, Chiara
dc.contributor.authorEveritt, Barry J
dc.contributor.authorBelin, David
dc.date.accessioned2021-10-15T23:31:29Z
dc.date.available2021-10-15T23:31:29Z
dc.date.issued2022-06-15
dc.identifier.issn0006-3223
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329450
dc.description.abstractBACKGROUND: The mechanisms through which drug-cue-induced negative affective states are involved in relapse have not been defined. We tested the hypothesis that in individuals having developed a dorsolateral striatum (DLS)-dependent cue-controlled cocaine-seeking habit, the loss of the opportunity to enact the drug-seeking response during abstinence results in an urge to act that exacerbates relapse severity mediated by negative urgency. METHODS: Eighty-seven male Sprague Dawley rats were trained to seek cocaine under the influence of the conditioned reinforcing properties of drug-paired cues or not. We investigated whether the tendency to relapse depended on the aversive state of withdrawal or instead on the loss of opportunity to perform the ingrained drug-seeking response after periods of abstinence. The striatal locus of control over cocaine seeking at baseline and relapse was investigated using in situ hybridization of the cellular activity marker C-fos and assessment of the sensitivity of instrumental drug seeking to dopamine receptor blockade in the dorsomedial striatum-dependent goal-directed and DLS-dependent habit systems. RESULTS: The development of a DLS-dependent cue-controlled cocaine-seeking habit prior to abstinence resulted in a marked increase in drug seeking at relapse, which was not motivated by a cocaine withdrawal state and was no longer dependent on the DLS habit system. Instead, it reflected the emergence of negative urgency caused by the prevention of the performance of the habit during abstinence and underpinned by transient engagement of the goal-directed system. CONCLUSIONS: These results show that ingrained cue-controlled drug-seeking habits increase the pressure to relapse.
dc.description.sponsorshipLeverhulme Trust
dc.languageen
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleNegative Urgency Exacerbates Relapse to Cocaine Seeking After Abstinence.
dc.typeArticle
prism.publicationDate2021
prism.publicationNameBiol Psychiatry
dc.identifier.doi10.17863/CAM.76898
dcterms.dateAccepted2021-10-08
rioxxterms.versionofrecord10.1016/j.biopsych.2021.10.009
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-10
dc.contributor.orcidFouyssac, Maxime [0000-0002-9496-5836]
dc.contributor.orcidEveritt, Barry [0000-0003-4431-6536]
dc.contributor.orcidBelin, David [0000-0002-7383-372X]
dc.identifier.eissn1873-2402
rioxxterms.typeJournal Article/Review
pubs.funder-project-idLeverhulme Trust (RPG-2016-117)
pubs.funder-project-idMedical Research Council (MR/N02530X/1)
cam.issuedOnline2021-10-20
cam.orpheus.successMon Oct 25 07:30:37 BST 2021 - Embargo updated
cam.orpheus.counter1
rioxxterms.freetoread.startdate2022-10-31


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International