Neostriatum neuronal TRPV1-signalling mediates striatal anandamide at high concentration facilitatory influence on neostriato-nigral dishinhibitory GABAergic connections

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dc.contributor.authorda Silva, Juliana Almeida
dc.contributor.authorAlmada, Rafael Carvalho [UNESP]
dc.contributor.authorFalconi-Sobrinho, Luiz Luciano
dc.contributor.authorPigatto, Glauce Regina
dc.contributor.authorHernandes, Paloma Molina [UNESP]
dc.contributor.authorCoimbra, Norberto Cysne
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.contributor.institutionBehavioural Neuroscience Institute (INeC)
dc.date.accessioned2023-07-29T13:59:48Z
dc.date.available2023-07-29T13:59:48Z
dc.date.issued2023-01-01
dc.description.abstractRationale: Several lines of evidence have demonstrated that the cannabinoid type 1 receptor (CB1) is found in the caudate nucleus and putamen (CPu) in addition to the substantia nigra pars reticulata (SNpr). Here, we investigated the role of endocannabinoid neuromodulation of striato-nigral disinhibitory projections on the activity of nigro-collicular GABAergic pathways that control the expression of unconditioned fear-related behavioural responses elicited by microinjections of the GABAA receptor selective antagonist bicuculline (BIC) in the deep layers of the superior colliculus (dlSC). Methods: Fluorescent neural tract tracers were deposited in either CPu or in SNpr. Wistar rats received injection of vehicle, anandamide (AEA), either at low (50 pmol) or high (100 pmol) concentrations in CPu followed by bicuculline microinjections in dlSC. Results: Connections between CPu, the SNpr and dlSC were demonstrated. The GABAA receptor blockade in dlSC elicited panic-like behaviour. AEA at the lowest concentration caused a panicolytic-like effect that was antagonised by the CPu pretreatment with AM251 at 100 pmol. AEA at the highest concentration caused a panicogenic-like effect that was antagonised by the CPu pretreatment with 6-iodonordihydrocapsaicin (6-I-CPS) at different concentrations (0.6, 6, 60 nmol). Conclusion: These findings suggest that while pre-synaptic CB1-signalling subserves an indirect facilitatory effect of AEA on striato-nigral pathways causing panicolytic-like responses through midbrain tectum enhanced activity, post-synaptic TRPV1-signalling in CPu mediates AEA direct activation of striato-nigral disinhibitory pathways resulting in increasing dlSC neurons activity and a panicogenic-like response. All these actions seem to depend on the interface with the nigro-collicular inhibitory GABAergic pathways.en
dc.description.affiliationRibeirão Preto Medical School of the University of São Paulo (FMRP-USP) Department of Pharmacology Laboratory of Neuroanatomy and Neuropsychobiology, São Paulo
dc.description.affiliationSão Paulo State University (UNESP) School of Science and Literature Department of Biological Sciences, São Paulo
dc.description.affiliationBehavioural Neuroscience Institute (INeC), São Paulo
dc.description.affiliationNAP-USP-Neurobiology of Emotions Research Centre (NuPNE) Ribeirão Preto Medical School of the University of São Paulo, São Paulo
dc.description.affiliationUnespSão Paulo State University (UNESP) School of Science and Literature Department of Biological Sciences, São Paulo
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipUnited States Pharmacopeia
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdCNPq: 130170/2009-7
dc.description.sponsorshipIdCNPq: 134267/2013-3
dc.description.sponsorshipIdCNPq: 142030/2020-1
dc.description.sponsorshipIdCNPq: 142844/2011-0
dc.description.sponsorshipIdCNPq: 145258/2015-7
dc.description.sponsorshipIdCNPq: 150124/2021-0
dc.description.sponsorshipIdCNPq: 2005.1.891.17.3
dc.description.sponsorshipIdFAPESP: 2007/01174-1
dc.description.sponsorshipIdCNPq: 2009/02458-9
dc.description.sponsorshipIdFAPESP: 2012/03798-0
dc.description.sponsorshipIdFAPESP: 2012/22681-7
dc.description.sponsorshipIdFAPESP: 2013/10984-8
dc.description.sponsorshipIdCNPq: 2015/10313-1
dc.description.sponsorshipIdFAPESP: 2017/11855-8
dc.description.sponsorshipIdFAPESP: 2018/03898-1
dc.description.sponsorshipIdFAPESP: 2019/01713-7
dc.description.sponsorshipIdFAPESP: 2019/05255-3
dc.description.sponsorshipIdFAPESP: 2020/15050-7
dc.description.sponsorshipIdCNPq: 2021/001-1
dc.description.sponsorshipIdCNPq: 301341/2015-0
dc.description.sponsorshipIdCNPq: 301905/2010-0
dc.description.sponsorshipIdCNPq: 302605/2021-5
dc.description.sponsorshipIdCNPq: 427397/2018-9
dc.description.sponsorshipIdCNPq: 470119/2004-7
dc.description.sponsorshipIdUnited States Pharmacopeia: IaPq2012–156-USP-12.1.25440.01.6
dc.description.sponsorshipIdCAPES: PNPD20131680-33002029012P3
dc.format.extent128-141
dc.identifierhttp://dx.doi.org/10.1016/j.brainresbull.2022.11.014
dc.identifier.citationBrain Research Bulletin, v. 192, p. 128-141.
dc.identifier.doi10.1016/j.brainresbull.2022.11.014
dc.identifier.issn1873-2747
dc.identifier.issn0361-9230
dc.identifier.scopus2-s2.0-85142516793
dc.identifier.urihttp://hdl.handle.net/11449/249004
dc.language.isoeng
dc.relation.ispartofBrain Research Bulletin
dc.sourceScopus
dc.subjectAnandamide
dc.subjectCaudate nucleus
dc.subjectDeep layers of superior colliculus
dc.subjectEndovanilloid receptors
dc.subjectStriatonigral-nigrotectal GABAergic pathways
dc.subjectUnconditioned fear
dc.titleNeostriatum neuronal TRPV1-signalling mediates striatal anandamide at high concentration facilitatory influence on neostriato-nigral dishinhibitory GABAergic connectionsen
dc.typeArtigo

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