title: Endocannabinoid signaling mechanisms in the substantia nigra pars reticulata modulate GABAergic nigrotectal pathways in mice threatened by urutu-cruzeiro venomous pit viper.
abstract: The substantia nigra pars reticulata (SNpr) is rich in γ-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 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 50pmol) 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.
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil; Institute of Neuroscience and Behaviour (INeC), Av. do Café, 2450, Ribeirão Preto, São Paulo, 14050-220, Brazil.
authors.forename: R C
authors.initials: RC
authors.lastname: Almada
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil.
authors.forename: C M
authors.initials: CM
authors.lastname: Roncon
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil; Institute of Neuroscience and Behaviour (INeC), Av. do Café, 2450, Ribeirão Preto, São Paulo, 14050-220, Brazil.
authors.forename: D H
authors.initials: DH
authors.lastname: Elias-Filho
authors.affiliation: Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo (FMRP-USP), Av. dos Bandeirantes, 3900, Ribeirão Preto, São Paulo 14049-900, Brazil; Institute of Neuroscience and Behaviour (INeC), Av. do Café, 2450, Ribeirão Preto, São Paulo, 14050-220, Brazil; NAP-USP-Neurobiology of Emotions Research Centre (NuPNE), Ribeirão Preto Medical School of the University of São Paulo, Ribeirão Preto, São Paulo, Brazil. Electronic address: nccoimbr@fmrp.usp.br.
authors.forename: N C
authors.initials: NC
authors.lastname: Coimbra
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D003435:Crotalid Venoms; D063388:Endocannabinoids / Q000378:metabolism* / Q000494:pharmacology; D004924:Escape Reaction / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000502:physiology* / Q000523:psychology; D007839:Functional Laterality; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D065842:Pars Compacta / Q000187:drug effects / Q000502:physiology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D003336:Tectum Mesencephali / Q000378:metabolism*; D017819:Viperidae; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D003435:Crotalid Venoms; D063388:Endocannabinoids; D058787:GABA-A Receptor Antagonists; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D016708:Synaptophysin; D005680:gamma-Aminobutyric Acid; C078814:anandamide; D001640:Bicuculline
keywords: Bothrops alternatus venomous snakes; dorsal periaqueductal gray matter (dPAG); endocannabinoids; panic-related behavior; substantia nigra pars reticulata (SNpr)