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dc.contributor.authorMar, ACen
dc.contributor.authorNilsson, SROen
dc.contributor.authorGamallo-Lana, Ben
dc.contributor.authorLei, Men
dc.contributor.authorDourado, Ten
dc.contributor.authorAlsio, Jen
dc.contributor.authorSaksida, Lisaen
dc.contributor.authorBussey, Timothyen
dc.contributor.authorRobbins, Trevoren
dc.date.accessioned2017-07-10T14:54:22Z
dc.date.available2017-07-10T14:54:22Z
dc.identifier.issn0033-3158
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/265235
dc.description.abstract$\textit{Rationale}$ Impairments in attention and inhibitory control are endophenotypic markers of neuropsychiatric disorders such as schizophrenia and represent key targets for therapeutic management. Robust preclinical models and assays sensitive to clinically relevant treatments are crucial for improving cognitive enhancement strategies. $\textit{Objectives}$ We assessed a rodent model with neural and behavioral features relevant to schizophrenia (gestational day 17 methylazoxymethanol acetate treatment (MAM-E17)) on a novel test of attention and executive function, and examined the impact of putative nootropic drugs. $\textit{Methods}$ MAM-E17 and sham control rats were trained on a novel touchscreen-based rodent continuous performance test (rCPT) designed to closely mimic the human CPT paradigm. Performance following acute, systemic treatment with an array of pharmacological compounds was investigated. $\textit{Results}$ Two cohorts of MAM-E17 rats were impaired on rCPT performance including deficits in sensitivity (d′) and increased false alarm rates (FARs). Sulpiride (0–30 mg/kg) dose-dependently reduced elevated FAR in MAM-E17 rats whereas low-dose modafinil (8 mg/kg) only improved d′ in sham controls. ABT-594 (5.9–19.4 μg/kg) and modafinil (64 mg/kg) showed expected stimulant-like effects, while LSN2463359 (5 mg/kg), RO493858 (10 mg/kg), atomoxetine (0.3–1 mg/kg), and sulpiride (30 mg/kg) showed expected suppressant effects on performance across all animals. Donepezil (0.1–1 mg/kg) showed near-significant enhancements in d′, and EVP-6124 (0.3–3 mg/kg) exerted no effects in the rCPT paradigm. $\textit{Conclusion}$ The MAM-E17 model exhibits robust and replicable impairments in rCPT performance that resemble attention and inhibitory control deficits seen in schizophrenia. Pharmacological profiles were highly consistent with known drug effects on cognition in preclinical and clinical studies. The rCPT is a sensitive and reliable tool with high translational potential for understanding the etiology and treatment of disorders affecting attention and executive dysfunction.
dc.description.sponsorshipThe research leading to these results has received support from the Innovative Medicine Initiative Joint Undertaking under grant agreement no. 115008 of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013). The Behavioural and Clinical Neuroscience Institute is co-funded by the Medical Research Council and the Wellcome Trust. BGL received funding support from the "La Caixa" Fellowship Postgraduate Programme. ML was supported by the Chinese Scholarship Council Joint PhD Program. JA received funding support from the Swedish Pharmaceutical Society and the Swedish Research Council (no. 350- 2012-230).
dc.language.isoenen
dc.publisherSpringer
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectattentionen
dc.subjectMAM-E17en
dc.subjectexecutive functionen
dc.subjecttouch screenen
dc.subjectbehavioral pharmacologyen
dc.subjectschizophreniaen
dc.subjectADHDen
dc.subjectanimal modelen
dc.titleMAM-E17 rat model impairments on a novel continuous performance task: effects of potential cognitive enhancing drugsen
dc.typeArticle
prism.publicationNamePsychopharmacologyen
dc.identifier.doi10.17863/CAM.11238
dcterms.dateAccepted2017-06-18en
rioxxterms.versionofrecord10.1007/s00213-017-4679-5en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2017-06-18en
dc.contributor.orcidRobbins, Trevor [0000-0003-0642-5977]
dc.identifier.eissn1432-2072
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idEC FP7 CP (115008)
pubs.funder-project-idMRC (G1000183)
cam.issuedOnline2017-07-26en
cam.orpheus.successThu Jan 30 12:53:28 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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