期刊
NEUROSCIENCE
卷 303, 期 -, 页码 503-514出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2015.06.048
关键词
substantia nigra pars reticulata (SNpr); dorsal periaqueductal gray matter (dPAG); endocannabinoids; panic-related behavior; Bothrops alternatus venomous snakes
资金
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2012/03798-0]
- Conselho Nacional de Pesquisa e Desenvolvimento Tecnologico (CNPq) [470119/2004-7]
- Fundacao de Apoio ao Ensino, Pesquisa e Assistencia do HC-FMRP-USP (FAEPA) [1291/97, 355/2000, 68/2001, 15/2003]
- Pro-Rectory of the University of Sao Paulo (USP) Research grant [IaPQ2012, NAP-USP-NuPNE-156]
- FAPESP [process 2012/22681-7, process 2012/23238-0]
- CNPq [process 301905/2010-0, process 501858/2005-9, process 500896/2008-9, process 505461/2010-2]
- FAPESP (TT-2) [process 02/01497-1]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [12/03798-0] Funding Source: FAPESP
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.
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