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dc.contributor.authorPuaud, Mickaël
dc.contributor.authorHiguera-Matas, Alejandro
dc.contributor.authorBrunault, Paul
dc.contributor.authorEveritt, Barry J
dc.contributor.authorBelin, David
dc.date.accessioned2020-08-03T23:31:48Z
dc.date.available2020-08-03T23:31:48Z
dc.date.issued2021-02-15
dc.identifier.issn0006-3223
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/308743
dc.description.abstractBACKGROUND: Individuals addicted to cocaine spend much of their time foraging for the drug. Pavlovian drug-associated conditioned stimuli exert a major influence on the initiation and maintenance of drug seeking often long into abstinence, especially when presented response-contingently, acting as conditioned reinforcers that bridge delays to drug use. The acquisition of cue-controlled cocaine seeking has been shown to depend on functional interactions between the basolateral amygdala (BLA) and the nucleus accumbens core (NAcC). However, the precise neuronal circuits underlying the acquisition of cue-controlled cocaine-seeking behavior have not been elucidated. METHODS: Here, we used a projection-specific Cre-dependent DREADD (designer receptor exclusively activated by designer drugs)-mediated causal approach to test the hypothesis that the direct projections from the BLA to the NAcC are required for the acquisition of cue-controlled cocaine-seeking behavior. RESULTS: In Sprague Dawley rats with Cre-mediated expression of the inhibitory DREADD hM4D(Gi) in the NAcC-projecting BLA neurons, treatment with clozapine N-oxide, but not vehicle, selectively prevented the impact of cocaine-associated conditioned reinforcers on cocaine seeking under a second-order schedule of reinforcement. This effect was attributable to the chemogenetic inhibition of the NAcC-projecting BLA neurons, as it was reversible, and it was absent in clozapine N-oxide-treated rats expressing an empty control virus. In contrast, chemogenetic inhibition of the anterior insula, which receives collateral projections from NAcC-projecting BLA neurons, was without effect. CONCLUSIONS: These data demonstrate that the acquisition of cue-controlled cocaine seeking that depends on the conditioned reinforcing effects of cocaine cues requires activity in the direct projections from the BLA to the NAcC.
dc.description.sponsorshipLeverhulme Trust
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectNucleus Accumbens
dc.subjectAnimals
dc.subjectRats
dc.subjectRats, Sprague-Dawley
dc.subjectCocaine
dc.subjectSelf Administration
dc.subjectCues
dc.subjectDrug-Seeking Behavior
dc.subjectBasolateral Nuclear Complex
dc.titleThe Basolateral Amygdala to Nucleus Accumbens Core Circuit Mediates the Conditioned Reinforcing Effects of Cocaine-Paired Cues on Cocaine Seeking.
dc.typeArticle
prism.endingPage365
prism.issueIdentifier4
prism.publicationDate2021
prism.publicationNameBiol Psychiatry
prism.startingPage356
prism.volume89
dc.identifier.doi10.17863/CAM.55832
dcterms.dateAccepted2020-07-27
rioxxterms.versionofrecord10.1016/j.biopsych.2020.07.022
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2021-02
dc.contributor.orcidPuaud, Mickael [0000-0002-7943-1801]
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.issuedOnline2020-08-05
cam.orpheus.successWed Aug 19 08:05:13 BST 2020 - Embargo updated
cam.orpheus.counter1
rioxxterms.freetoread.startdate2021-08-31


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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