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

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Autor(es):
Silva, Juliana Almeida da ; Almada, Rafael Carvalho ; Falconi-Sobrinho, Luiz Luciano ; Pigatto, Glauce Regina ; Hernandes, Paloma Molina ; Coimbra, Norberto Cysne
Número total de Autores: 6
Tipo de documento: Artigo Científico
Fonte: Brain Research Bulletin; v. 192, p. 14-pg., 2023-01-01.
Resumo

Rationale: 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 re-sponses 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. (AU)

Processo FAPESP: 20/15050-7 - Estudo do papel da sinalização endocanabinoide e endovaniloide no paleoestriado, na atividade do duplo elo conectivo GABAérgico neoestriado-pálido-nigro-tectal durante a organização do medo instintivo de animais confrontados com serpentes
Beneficiário:Norberto Cysne Coimbra
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 07/01174-1 - Estudo do envolvimento do sistema opióide, serotoninérgico e noradrenérgico do sistema endógeno de inibição de dor em processos antinociceptivos induzidos por reações de fuga orientada evocada pela estimulação química do hipotálamo medial
Beneficiário:Norberto Cysne Coimbra
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/03798-0 - Envolvimento de receptores opióides e endocanabinóides da substância negra na modulação da atividade da via GABAérgica nigro-tectal durante a organização do comportamento de defesa eliciado por roedores confrontados com serpentes veneníferas
Beneficiário:Norberto Cysne Coimbra
Modalidade de apoio: Auxílio à Pesquisa - Regular