Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments

Castro Zavala, Adriana, 1988-; Alegre Zurano, Laia; Cantacorps Centellas, Lídia, 1991-; Gallego-Landin, Ines; Welz, Patrick-Simon; Benitah, Salvador A.; Valverde Granados, Olga

Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments

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dc.contributor.author Castro Zavala, Adriana, 1988-
dc.contributor.author Alegre Zurano, Laia
dc.contributor.author Cantacorps Centellas, Lídia, 1991-
dc.contributor.author Gallego-Landin, Ines
dc.contributor.author Welz, Patrick-Simon
dc.contributor.author Benitah, Salvador A.
dc.contributor.author Valverde Granados, Olga
dc.date.accessioned 2022-09-06T07:18:21Z
dc.date.available 2022-09-06T07:18:21Z
dc.date.issued 2022
dc.description.abstract Brain and Muscle Arnt-like Protein 1 (BMAL1) is an essential component of the molecular clock underlying circadian rhythmicity. Its function has been recently associated with mood and reward processing alterations. We investigated the behavioural and neurobiological impact of Bmal1 gene deletion in mice, and how this could affect rewarding effects of cocaine. Additionally, key clock genes and components of the dopamine system were assessed in several brain areas. Our results evidence behavioural alterations in Bmal1-KO mice, including changes in locomotor activity with impaired habituation to environments, short-term memory and social recognition impairments. In addition, Bmal1-KO mice experienced reduced cocaine-induced sensitisation and rewarding effects of cocaine as well as reduced cocaine-seeking behaviour. Furthermore, Bmal1 deletion influenced the expression of other clock-related genes in the mPFC and striatum, as well as alterations in the expression of dopaminergic elements. Overall, the present article offers a novel and extensive characterisation of Bmal1-KO animals. We suggest that reduced cocaine's rewarding effects in these mutant mice might be related to Bmal1 role as an expression regulator of MAO and TH, two essential enzymes involved in dopamine metabolism.
dc.description.sponsorship This study was supported by the Ministerio de Ciencia e Innovacion (grant number PID2019-104077RB-100/AEI/10.13039/501100011033), Ministerio de Sanidad (Retic-ISCIII, grant number RD16/017/010; RICORS, grant number RD21/0009/0001, and Plan Nacional sobre Drogas 2018/007). L.A.-Z. and I.G.-L. received a FPI grants (BES-2017-080066 and PRE2020-091923) from the Ministerio de Economia y Competividad. P.S.W. was supported by grant RYC2019-026661-I funded by MCIN/AEI/10.13039/501100011033 and by "ESF Investing in your future". The Department of Medicine and Health Sciences (MELIS-UPF) is a “Unidad de Excelencia María de Maeztu” funded by the AEI (CEX2018-000792-M). O.V. is recipient of an ICREA Academia Award (Institució Catalana de Recerca i Estudis Avançats, Generalitat de Catalunya).
dc.format.mimetype application/pdf
dc.identifier.citation Castro-Zavala A, Alegre-Zurano L, Cantacorps L, Gallego-Landin I, Welz PS, Benitah SA, Valverde O. Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments. Biomed Pharmacother. 2022 Jun 29;153:113333. DOI: 10.1016/j.biopha.2022.113333
dc.identifier.doi http://dx.doi.org/10.1016/j.biopha.2022.113333
dc.identifier.issn 0753-3322
dc.identifier.uri http://hdl.handle.net/10230/53997
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Biomed Pharmacother. 2022 Jun 29;153:113333
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-104077RB-100
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BES-2017-080066
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PRE2020-091923
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RYC2019-026661-I
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.keyword Bmal1
dc.subject.keyword Circadian rhythms
dc.subject.keyword Cocaine
dc.subject.keyword GluA1
dc.subject.keyword GluA2
dc.title Bmal1-knockout mice exhibit reduced cocaine-seeking behaviour and cognitive impairments
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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