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dc.contributor.authorHailwood, Jonathan M
dc.contributor.authorHeath, Christopher J
dc.contributor.authorPhillips, Benjamin U
dc.contributor.authorRobbins, Trevor W
dc.contributor.authorSaksida, Lisa M
dc.contributor.authorBussey, Timothy J
dc.date.accessioned2018-12-15T00:30:47Z
dc.date.available2018-12-15T00:30:47Z
dc.date.issued2019-05
dc.identifier.issn0893-133X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/286996
dc.description.abstractDisruptions to motivated behaviour are a highly prevalent and severe symptom in a number of neuropsychiatric and neurodegenerative disorders. Current treatment options for these disorders have little or no effect upon motivational impairments. We assessed the contribution of muscarinic acetylcholine receptors to motivated behaviour in mice, as a novel pharmacological target for motivational impairments. Touchscreen progressive ratio (PR) performance was facilitated by the nonselective muscarinic receptor antagonist scopolamine as well as the more subtype-selective antagonists biperiden (M1) and tropicamide (M4). However, scopolamine and tropicamide also produced increases in non-specific activity levels, whereas biperiden did not. A series of control tests suggests the effects of the mAChR antagonists were sensitive to changes in reward value and not driven by changes in satiety, motor fatigue, appetite or perseveration. Subsequently, a sub-effective dose of biperiden was able to facilitate the effects of amphetamine upon PR performance, suggesting an ability to enhance dopaminergic function. Both biperiden and scopolamine were also able to reverse a haloperidol-induced deficit in PR performance, however only biperiden was able to rescue the deficit in effort-related choice (ERC) performance. Taken together, these data suggest that the M1 mAChR may be a novel target for the pharmacological enhancement of effort exertion and consequent rescue of motivational impairments. Conversely, M4 receptors may inadvertently modulate effort exertion through regulation of general locomotor activity levels.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectMice
dc.subjectDisease Models, Animal
dc.subjectBiperiden
dc.subjectHaloperidol
dc.subjectScopolamine
dc.subjectTropicamide
dc.subjectReceptor, Muscarinic M1
dc.subjectReceptor, Muscarinic M4
dc.subjectMuscarinic Antagonists
dc.subjectAntipsychotic Agents
dc.subjectBehavior, Animal
dc.subjectMotivation
dc.subjectPsychomotor Performance
dc.subjectApathy
dc.subjectCognitive Dysfunction
dc.titleBlockade of muscarinic acetylcholine receptors facilitates motivated behaviour and rescues a model of antipsychotic-induced amotivation.
dc.typeArticle
prism.endingPage1075
prism.issueIdentifier6
prism.publicationDate2019
prism.publicationNameNeuropsychopharmacology
prism.startingPage1068
prism.volume44
dc.identifier.doi10.17863/CAM.34305
dcterms.dateAccepted2018-11-17
rioxxterms.versionofrecord10.1038/s41386-018-0281-8
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-05
dc.contributor.orcidHailwood, Jonathan M [0000-0002-5835-2143]
dc.identifier.eissn1740-634X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMRC (1505392)
cam.issuedOnline2018-11-27
rioxxterms.freetoread.startdate2019-05-27


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