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Chronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivity

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dc.contributor.authorMouro, Francisco
dc.contributor.authorRibeiro, Joaquim A.
dc.contributor.authorSebastião, Ana M
dc.contributor.authorDawson, Neil
dc.date.accessioned2021-10-20T15:21:51Z
dc.date.available2021-10-20T15:21:51Z
dc.date.issued2018
dc.description© 2018 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.pt_PT
dc.description.abstractElucidating how cannabinoids affect brain function is instrumental for the development of therapeutic tools aiming to mitigate 'on target' side effects of cannabinoid-based therapies. A single treatment with the cannabinoid receptor agonist, WIN 55,212-2, disrupts recognition memory in mice. Here, we evaluate how prolonged, intermittent (30 days) exposure to WIN 55,212-2 (1 mg/kg) alters recognition memory and impacts on brain metabolism and functional connectivity. We show that chronic, intermittent treatment with WIN 55,212-2 disrupts recognition memory (Novel Object Recognition Test) without affecting locomotion and anxiety-like behaviour (Open Field and Elevated Plus Maze). Through 14 C-2-deoxyglucose functional brain imaging we show that chronic, intermittent WIN 55,212-2 exposure induces hypometabolism in the hippocampal dorsal subiculum and in the mediodorsal nucleus of the thalamus, two brain regions directly involved in recognition memory. In addition, WIN 55,212-2 exposure induces hypometabolism in the habenula with a contrasting hypermetabolism in the globus pallidus. Through the application of the Partial Least Squares Regression (PLSR) algorithm to the brain imaging data, we observed that prolonged WIN 55,212-2 administration alters functional connectivity in brain networks that underlie recognition memory, including that between the hippocampus and prefrontal cortex, the thalamus and prefrontal cortex, and between the hippocampus and the perirhinal cortex. In addition, our results support disturbed lateral habenula and serotonin system functional connectivity following WIN 55,212-2 exposure. Overall, this study provides new insight into the functional mechanisms underlying the impact of chronic cannabinoid exposure on memory and highlights the serotonin system as a particularly vulnerable target.pt_PT
dc.description.sponsorshipThis work was supported by LISBOA-01-0145-FEDER-007391, project co-funded by FEDER through POR Lisboa 2020 (Programa Operacional Regional de Lisboa) from PORTUGAL 2020 and Fundação para a Ciência e Tecnologia (FCT), by an FCT project (Fundação para a Ciência e a Tecnologia, PTDC/DTP-FTO/3346/2014) and by a Twinning action (SynaNet) from the EU H2020 Programme (project number: 692340), which covered short-term scientific missions of FMM at ND laboratory and of ND at AMS laboratory. FMM was in receipt of SFRH/BD/89582/2012 FTC fellowship.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Neurochem. 2018 Oct;147(1):71-83pt_PT
dc.identifier.doi10.1111/jnc.14549pt_PT
dc.identifier.eissn1471-4159
dc.identifier.issn0022-3042
dc.identifier.urihttp://hdl.handle.net/10451/49959
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley & Sons, Inc.pt_PT
dc.relationLISBOA-01-0145-FEDER-007391pt_PT
dc.relationSynaptic mechanisms involved in the brain cannabinoid actions and their modulation by adenosine receptors: implications for memory and mood control
dc.relationNeurologic and Psychiatric Disorders: from synapses to networks
dc.relationINTERACTION BETWEEN ADENOSINE A2A RECEPTORS AND CANNABINOID CB1 RECEPTORS AT THE HIPPOCAMPUS: CONSEQUENCES FOR PLASTICITY AND MEMORY
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/14714159pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectCannabinoidspt_PT
dc.subjectChronicpt_PT
dc.subjectFunctional connectivitypt_PT
dc.subjectRecognition memorypt_PT
dc.titleChronic, intermittent treatment with a cannabinoid receptor agonist impairs recognition memory and brain network functional connectivitypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleSynaptic mechanisms involved in the brain cannabinoid actions and their modulation by adenosine receptors: implications for memory and mood control
oaire.awardTitleNeurologic and Psychiatric Disorders: from synapses to networks
oaire.awardTitleINTERACTION BETWEEN ADENOSINE A2A RECEPTORS AND CANNABINOID CB1 RECEPTORS AT THE HIPPOCAMPUS: CONSEQUENCES FOR PLASTICITY AND MEMORY
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FDTP-FTO%2F3346%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/692340/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F89582%2F2012/PT
oaire.citation.endPage83pt_PT
oaire.citation.issue1pt_PT
oaire.citation.startPage71pt_PT
oaire.citation.titleJournal of Neurochemistrypt_PT
oaire.citation.volume147pt_PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamH2020
person.familyNameMouro
person.familyNameRibeiro
person.familyNameSebastião
person.givenNameFrancisco
person.givenNameJoaquim
person.givenNameAna M
person.identifier548147
person.identifier.ciencia-id081F-2518-907F
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.orcid0000-0002-7141-8418
person.identifier.orcid0000-0002-9330-3507
person.identifier.orcid0000-0001-9030-6115
person.identifier.scopus-author-id35498669400
person.identifier.scopus-author-id7004409879
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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