ENDOCANNABINOID SIGNALING MECHANISMS IN THE SUBSTANTIA NIGRA PARS RETICULATA MODULATE GABAergic NIGROTECTAL PATHWAYS IN MICE THREATENED BY URUTU-CRUZEIRO VENOMOUS PIT VIPER

Autor(es)

Almada, R. C. ^{[1, 2]} ; Roncon, C. M. ^[2] ; Elias-Filho, D. H. ^{[1, 2]} ; Coimbra, N. C. ^{[1, 2, 3]}

Afiliação do(s) autor(es)

^[1] Inst Neurosci & Behav INeC, BR-14050220 Sao Paulo - Brazil

^[2] Univ Sao Paulo FMRP USP, Ribeirao Preto Med Sch, Dept Pharmacol, Lab Neuroanat & Neuropsychobiol, BR-14049900 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Ribeirao Preto Med Sch, NAP USP Neurobiol Emot Res Ctr NuPNE, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Neuroscience; v. 303, p. 503-514, SEP 10 2015.
• Citações Web of Science: 19

Resumo

The substantia nigra pars reticulata (SNpr) is rich in gamma-aminobutyric acid (GABA)-ergic neurons and connected to the mesencephalic tectum (MT) structures, such as the superior colliculus and dorsal periaqueductal gray matter. The SNpr presents a high density of cannabinoid receptors (CBRs), suggesting a possible regulatory role that is played by endocannabinoids (eCBs) in the ventral mesencephalon. The present study investigated the involvement of SNpr eCB mechanisms in nigrotectal pathways in the expression of defensive behavior associated with instinctive fear and panic reactions in mice that are confronted with the venomous Viperidae snake Bothrops alternatus. The localization of CB1 receptors (CB1RS) and synaptophysin glycoprotein in the SNpr was also evaluated. Administration of the GABA(A) receptor antagonist bicuculline in the MT increased defensive responses to the snake that are related to panic, such as freezing and no escape reactions, sometimes toward the snake itself. Mice that were pretreated with anandamide (5 or 50 pmol) in the SNpr, followed by an injection of physiological saline or bicuculline in the MT, exhibited significant decreases in the expression of alertness, freezing, and escape responses. Immunofluorescence showed the presence of fibers that were rich in CB1RS and synaptophysin in the SNpr, indicating that these receptors appear to be located mainly in presynaptic terminals in the striatonigral pathway. These findings suggest that eCB mechanisms in the SNpr facilitate the activity of nigrotectal GABAergic pathways, modulating the activity of striatonigral links during the elaboration and organization of innate fear and panic-like responses in threatening situations. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 12/23238-0 - Avaliação de mecanismos cooperativos entre os sistemas opioidérgico e o serotoninérgico na substância cinzenta periaqueductal dorsal nos efeitos de antidepressivos
• Beneficiário: Camila Marroni Roncon
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/22681-7 - Envolvimento de Receptores Opioides e Endocanabinoides da Substância Negra, Parte Reticulada, na Modulação da Atividade da Via GABAérgica Nigro-tectal durante a Organização do Comportamento Defensivo de Camundongos Confrontados com Serpentes Veneníferas
• Beneficiário: Rafael Carvalho Almada
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 02/01497-1 - Estudo do envolvimento do núcleo magno da rafe, do núcleo gigantocelular e núcleo pré-tectal anterior, e de receptores opiódes, kappa e delta serotoninérgicos 5HT2/1C, e noradrenérgicos alfa, beta, na analgesia pós-cital: um estudo neuroanatômico e neuropsicofisiológico em um modelo experimental de epilepsia
• Beneficiário: Daoud Hibrahim Elias Filho
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• 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