Orexin 1 and 2 Receptors in the Prelimbic Cortex Modulate Threat Valuation

dc.contributor.authorSoares, Victor P.M.N. [UNESP]
dc.contributor.authorde Andrade, Telma G.C.S. [UNESP]
dc.contributor.authorCanteras, Newton S.
dc.contributor.authorCoimbra, Norberto C.
dc.contributor.authorWotjak, Carsten T.
dc.contributor.authorAlmada, Rafael C. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionMax Planck Institute of Psychiatry
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionBehavioural Neuroscience Institute (INeC)
dc.contributor.institutionBoehringer Ingelheim Pharmaceuticals Die Gesellschaft mit Beschränkter Haftung & Compagnie Kommanditgesellschaft
dc.date.accessioned2022-04-29T08:45:34Z
dc.date.available2022-04-29T08:45:34Z
dc.date.issued2021-08-01
dc.description.abstractThe ability to distinguish between threatening (repulsors), neutral and appetitive stimuli (attractors) stimuli is essential for survival. The orexinergic neurons of hypothalamus send projections to the limbic structures, such as different subregions of the medial prefrontal cortex (mPFC), suggesting that the orexinergic mechanism in the prelimbic cortex (PL) is involved in the processing of fear and anxiety. We investigated the role of orexin receptors type 1 (OX1R) and type 2 (OX2R) in the PL in such processes upon confrontation with an erratically moving robo-beetle in mice. The selective blockade of OX1R and OX2R in the PL with SB 334867 (3, 30, 300 nM) and TCS OX2 29 (3, 30, 300 nM), respectively, did not affect general exploratory behavior or reactive fear such as avoidance, jumping or freezing, but significantly enhances tolerance and approach behavior at the highest dose of each antagonist tested (300 nM). We interpret these findings as evidence for an altered cognitive appraisal of the potential threatening stimulus. Consequently, the orexin system seems to bias the perception of stimuli towards danger or threat via OX1R and OX2R in the PL.en
dc.description.affiliationDepartment of Biological Sciences School of Sciences Humanities and Languages of the São Paulo State University (UNESP)
dc.description.affiliationNeuronal Plasticity Research Group Max Planck Institute of Psychiatry
dc.description.affiliationDepartment of Pharmacology Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP)
dc.description.affiliationDepartment of Anatomy Biomedical Sciences Institute of the University of São Paulo (ICB-USP)
dc.description.affiliationBehavioural Neuroscience Institute (INeC)
dc.description.affiliationNAP-USP-Neurobiology of Emotions Research Centre (NuPNE) Ribeirão Preto Medical School of the University of São Paulo
dc.description.affiliationCentral Nervous System Diseases Research Boehringer Ingelheim Pharmaceuticals Die Gesellschaft mit Beschränkter Haftung & Compagnie Kommanditgesellschaft
dc.description.affiliationUnespDepartment of Biological Sciences School of Sciences Humanities and Languages of the São Paulo State University (UNESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent158-167
dc.identifierhttp://dx.doi.org/10.1016/j.neuroscience.2021.06.006
dc.identifier.citationNeuroscience, v. 468, p. 158-167.
dc.identifier.doi10.1016/j.neuroscience.2021.06.006
dc.identifier.issn1873-7544
dc.identifier.issn0306-4522
dc.identifier.scopus2-s2.0-85109117727
dc.identifier.urihttp://hdl.handle.net/11449/231471
dc.language.isoeng
dc.relation.ispartofNeuroscience
dc.sourceScopus
dc.subjectanxiety
dc.subjectbeetle mania task
dc.subjectcognitive judgment bias
dc.subjectfear
dc.subjectmedial prefrontal cortex
dc.subjectorexin receptors
dc.titleOrexin 1 and 2 Receptors in the Prelimbic Cortex Modulate Threat Valuationen
dc.typeArtigo

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