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dc.contributor.authorNilsson, Simon RO
dc.contributor.authorHeath, Christopher J
dc.contributor.authorTakillah, Samir
dc.contributor.authorDidienne, Steve
dc.contributor.authorFejgin, Kim
dc.contributor.authorNielsen, Vibeke
dc.contributor.authorNielsen, Jacob
dc.contributor.authorSaksida, Lisa M
dc.contributor.authorMariani, Jean
dc.contributor.authorFaure, Philippe
dc.contributor.authorDidriksen, Michael
dc.contributor.authorRobbins, Trevor W
dc.contributor.authorBussey, Timothy J
dc.contributor.authorMar, Adam C
dc.date.accessioned2019-01-15T00:31:18Z
dc.date.available2019-01-15T00:31:18Z
dc.date.issued2018-11-14
dc.identifier.issn2158-3188
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287993
dc.description.abstractThe 22q11.2 deletion syndrome (22q11.2DS) confers high risk of neurodevelopmental disorders such as schizophrenia and attention-deficit hyperactivity disorder. These disorders are associated with attentional impairment, the remediation of which is important for successful therapeutic intervention. We assessed a 22q11.2DS mouse model (Df(h22q11)/+) on a touchscreen rodent continuous performance test (rCPT) of attention and executive function that is analogous to human CPT procedures. Relative to wild-type littermates, Df(h22q11)/+ male mice showed impaired attentional performance as shown by decreased correct response ratio (hit rate) and a reduced ability to discriminate target stimuli from non-target stimuli (discrimination sensitivity, or d'). The Df(h22q11)/+ model exhibited decreased prefrontal cortical-hippocampal oscillatory synchrony within multiple frequency ranges during quiet wakefulness, which may represent a biomarker of cognitive dysfunction. The stimulant amphetamine (0-1.0 mg/kg, i.p.) dose-dependently improved d' in Df(h22q11)/+ mice whereas the highest dose of modafinil (40 mg/kg, i.p.) exacerbated their d' impairment. This is the first report to directly implicate attentional impairment in a 22q11.2DS mouse model, mirroring a key endophenotype of the human disorder. The capacity of the rCPT to detect performance impairments in the 22q11.2DS mouse model, and improvement following psychostimulant-treatment, highlights the utility and translational potential of the Df(h22q11)/+ model and this automated behavioral procedure.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectHippocampus
dc.subjectPrefrontal Cortex
dc.subjectAnimals
dc.subjectMice, Transgenic
dc.subjectMice
dc.subjectDiGeorge Syndrome
dc.subjectDisease Models, Animal
dc.subjectAmphetamine
dc.subjectCentral Nervous System Stimulants
dc.subjectBehavior, Animal
dc.subjectPsychomotor Performance
dc.subjectAttention
dc.subjectMale
dc.subjectExecutive Function
dc.subjectElectroencephalography Phase Synchronization
dc.subjectCognitive Dysfunction
dc.subjectModafinil
dc.titleContinuous performance test impairment in a 22q11.2 microdeletion mouse model: improvement by amphetamine.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameTransl Psychiatry
prism.startingPage247
prism.volume8
dc.identifier.doi10.17863/CAM.30609
dcterms.dateAccepted2018-10-05
rioxxterms.versionofrecord10.1038/s41398-018-0295-3
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-11-14
dc.contributor.orcidTakillah, Samir [0000-0002-2345-7762]
dc.contributor.orcidMariani, Jean [0000-0002-2701-1581]
dc.identifier.eissn2158-3188
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (G1000183)
pubs.funder-project-idEuropean Commission (115008)
pubs.funder-project-idMedical Research Council (G0001354)
cam.issuedOnline2018-11-14


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