Endocannabinoid signaling mechanisms in the substantia nigra pars reticulata modulate GABAergic nigrotectal pathways in mice threatened by urutu-cruzeiro venomous pit viper snake.

The substantia nigra pars reticulata (SNpr) is rich in -aminobutyric acid (GABA)-ergic neurons and connected to 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 by the venomous pit viper snake Bothrops alternatus. The localization of CB1 receptors (CB1RS) and synaptophysin glycoprotein in the SNpr was also evaluated. Administration of the GABAA receptor antagonist bicuculline in the MT increased defensive responses to the snake that are related to panic, such as freezing and non-oriented 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 modulate the activity of nigrotectal GABAergic pathways, facilitating the activity of striatonigral links during the elaboration and organization of innate fear and panic-like responses in threatening situations.
Copyright © 2015. Published by Elsevier Ltd.