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dc.contributor.authorHorst, Nicole K
dc.contributor.authorJupp, Bianca
dc.contributor.authorRoberts, Angela C
dc.contributor.authorRobbins, Trevor W
dc.date.accessioned2018-12-12T00:31:14Z
dc.date.available2018-12-12T00:31:14Z
dc.date.issued2019-02
dc.identifier.issn0893-133X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286708
dc.description.abstractBehavioral flexibility, which allows organisms to adapt their actions in response to environmental changes, is impaired in a number of neuropsychiatric conditions, including obsessive-compulsive disorder and addiction. Studies in human subjects and monkeys have reported correlations between individual differences in dopamine D2-type receptor (D2R) levels in the caudate nucleus and performance in a discrimination reversal task, in which established contingent relationships between abstract stimuli and rewards (or punishments) are reversed. Global genetic deletion of the D2R in mice disrupts reversal performance, indicating a likely causal role for this receptor in supporting flexible behaviors. To directly examine the specific role of caudate D2-type receptors in reversal performance, the D2/3/4R agonist quinpirole was infused via chronic indwelling cannulae into the medial caudate of male and female marmoset monkeys performing a touchscreen-based serial discrimination reversal task. Given prior evidence for dose-dependent effects of quinpirole and other dopaminergic drugs, a full dose-response curve was established. Individually, marmosets displayed marked differences in behavioral sensitivity to specific doses of intra-caudate quinpirole. Collectively, they exhibited a behaviorally specific bi-phasic deficit in reversal learning, being consistently impaired at both relatively low and high doses of quinpirole. However, intermediate doses of intra-caudate quinpirole produced significant improvement in reversal performance. These data support previous human and monkey neuroimaging studies by providing causal evidence of a U-shaped function describing how dopamine modulates cognitive flexibility in the primate striatum.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCaudate Nucleus
dc.subjectAnimals
dc.subjectCallithrix
dc.subjectQuinpirole
dc.subjectReceptors, Dopamine D2
dc.subjectDopamine Agonists
dc.subjectBehavior, Animal
dc.subjectDiscrimination Learning
dc.subjectReversal Learning
dc.subjectSerial Learning
dc.subjectDose-Response Relationship, Drug
dc.subjectFemale
dc.subjectMale
dc.titleD2 receptors and cognitive flexibility in marmosets: tri-phasic dose-response effects of intra-striatal quinpirole on serial reversal performance.
dc.typeArticle
prism.endingPage571
prism.issueIdentifier3
prism.publicationDate2019
prism.publicationNameNeuropsychopharmacology
prism.startingPage564
prism.volume44
dc.identifier.doi10.17863/CAM.34015
dcterms.dateAccepted2018-10-24
rioxxterms.versionofrecord10.1038/s41386-018-0272-9
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-02
dc.contributor.orcidHorst, Nicole K [0000-0002-7145-8911]
dc.identifier.eissn1740-634X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (104631/Z/14/Z)
pubs.funder-project-idMedical Research Council (MR/J012084/1)
pubs.funder-project-idMedical Research Council (G1000183)
pubs.funder-project-idMedical Research Council (G0001354)
cam.issuedOnline2018-11-15
datacite.issupplementedby.urlhttps://doi.org/10.17863/CAM.32242


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