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Involvement of Opioid and Endocanabinoid Receptors of the Substantia Nigra, Pars Reticulata, in the Modulation of the Activity of Nigro-Tectal GABAergic Pathways during the Organization of Defensive Behaviour of Mice Confronted with Venomous Snakes

Grant number: 12/22681-7
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): August 01, 2013
Effective date (End): July 27, 2017
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Norberto Cysne Coimbra
Grantee:Rafael Carvalho Almada
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):15/09116-7 - Role of glucocorticoid, endocannabinoid and noradrenaline interactions during aversive conditioning in mice, BE.EP.PD

Abstract

The study of the neuropsychopharmacological bases of the fear- and panic-related behaviour has been the focus of several scientific researches. The mesencephalic tectum (MT) has been considered as responsible for the control of defensive responses evoked during threatening situations. The deep layers of the superior colliculus (dlSC) and the dorsal columns of the periaqueductal grey matter (dPAG) have been considered important structures for the elaboration of innate fear and defensive behaviour. The substantia nigra, pars reticulata (SNpr), is known to send inputs to the intermediate layers of the superior colliculus (ilSC) that can work as a sensory channel to dorsal midbrain neurons responsible for the elaboration of defensive responses in more ventral regions of this neural substrate. The dorsal mesencephalon, however, is connected to both compacta and reticulata divisions of the substantia nigra, through inputs rich in endogenous opioid peptides. This mesencephalic structure is also rich in CB1 endocannabinoid receptors, with putative involvement in this neural system that is known for these interactive properties with the opioid system, and has been the focus of interest of scientific community. The purpose of the present work is to investigate the role of µ receptors, as well as CB1-endocannabinoid receptors of SNpr, rich in GABAergic neurons connected to the mesencephalic tectum, in the modulation of defensive behaviour related to instinctive fear and panic reactions. Thus, it will be studied the effect of microinjections of µ-opioid receptors selective antagonists, CB1-endocannabinoid receptors selective antagonists into the SNpr on the elaboration of the defensive behaviour elaborated by dorsal mesencephalon induced by GABAA receptor selective blockade in the dlSC/dPAG of Wistar rats confronted with Bothrops jararaca .

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Scientific publications (11)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DA SILVA, JULIANA ALMEIDA; BIAGIONI, AUDREY FRANCESCHI; ALMADA, RAFAEL CARVALHO; DE FREITAS, RENATO LEONARDO; COIMBRA, NORBERTO CYSNE. Panicolytic-like effects caused by substantia nigra pars reticulata pretreatment with low doses of endomorphin-1 and high doses of CTOP or the NOP receptors antagonist JTC-801 in male Rattus norvegicus. Psychopharmacology, v. 234, n. 20, p. 3009-3025, . (12/03798-0, 13/12916-0, 09/02458-9, 07/01174-1, 09/54014-7, 09/17258-5, 17/11855-8, 14/10742-7, 12/22681-7, 10/15140-4, 15/10313-1, 14/11869-0)
DA SILVA, JULIANA ALMEIDA; BIAGIONI, AUDREY FRANCISCO; ALMADA, RAFAEL CARVALHO; DE SOUZA CRIPPA, JOSE ALEXANDRE; CECILIO HALLAK, JAIME EDUARDO; ZUARDI, ANTONIO WALDO; COIMBRA, NORBERTO CYSNE. Dissociation between the panicolytic effect of cannabidiol microinjected into the substantia nigra, pars reticulata, and fear-induced antinociception elicited by bicuculline administration in deep layers of the superior colliculus: The role of CB1-cannabinoid receptor in the ventral mesencephalon. European Journal of Pharmacology, v. 758, p. 153-163, . (12/03798-0, 09/02458-9, 07/01174-1, 09/54014-7, 14/10742-7, 12/22681-7, 10/15140-4)
CALVO, FABRICIO; ALMADA, RAFAEL CARVALHO; DOS ANJOS-GARCIA, TAYLLON; FALCONI-SOBRINHO, LUIZ LUCIANO; PASCHOALIN-MAURIN, TATIANA; BAZAGLIA-DE-SOUSA, GUILHERME; MEDEIROS, PRISCILA; DA SILVA, JULIANA ALMEIDA; LOBAO-SOARES, BRUNO; COIMBRA, NORBERTO CYSNE. Panicolytic-like effect of mu(1)-opioid receptor blockade in the inferior colliculus of prey threatened by Crotalus durissus terrificus pit vipers. JOURNAL OF PSYCHOPHARMACOLOGY, v. 33, n. 5, p. 577-588, . (12/03798-0, 09/02458-9, 07/01174-1, 12/25167-2, 13/10984-8, 17/13560-5, 17/11855-8, 12/22681-7, 15/10313-1)
CALVO, FABRICIO; ALMADA, RAFAEL CARVALHO; DA SILVA, JULIANA ALMEIDA; MEDEIROS, PRISCILA; SOARES, JR., RAIMUNDO DA SILVA; DE PAIVA, YARA BEZERRA; RONCON, CAMILA MARRONI; COIMBRA, NORBERTO CYSNE. The Blockade of mu(1)- and kappa-Opioid Receptors in the Inferior Colliculus Decreases the Expression of Panic Attack-Like Behaviours Induced by Chemical Stimulation of the Dorsal Midbrain. NEUROPSYCHOBIOLOGY, v. 78, n. 4, p. 218-228, . (09/54014-7, 12/23238-0, 15/10313-1, 09/02458-9, 07/01174-1, 12/25167-2, 12/03798-0, 17/13560-5, 12/22681-7)
DA SILVA, JULIANA ALMEIDA; ALMADA, RAFAEL CARVALHO; DE PAIVA, YARA BEZERRA; COIMBRA, NORBERTO CYSNE. Endocannabinoid neuromodulation in the neostriatum decreases the GABAergic striato-nigral disinhibitory function and increases the nigro-collicular inhibitory pathway activity. JOURNAL OF NEURAL TRANSMISSION, v. 127, n. 8, . (19/01713-7, 17/11855-8, 15/10313-1, 09/02458-9, 07/01174-1, 12/03798-0, 18/03898-1, 12/22681-7)
COIMBRA, NORBERTO CYSNE; CALVO, FABRICIO; ALMADA, RAFAEL CARVALHO; FREITAS, RENATO LEONARDO; PASCHOALIN-MAURIN, TATIANA; DOS ANJOS-GARCIA, TAYLLON; ELIAS-FILHO, DAOUD HIBRAHIM; UBIALI, WALTER ADRIANO; LOBAO-SOARES, BRUNO; TRACEY, IRENE. OPIOID NEUROTRANSMISSION MODULATES DEFENSIVE BEHAVIOR AND FEAR-INDUCED ANTINOCICEPTION IN DANGEROUS ENVIRONMENTS. Neuroscience, v. 354, p. 178-195, . (12/03798-0, 07/01174-1, 12/22681-7)
BASSI, G. S.; CARVALHO, M. C.; ALMADA, R. C.; BRANDAO, M. L.. Inhibition of substance P-induced defensive behavior via neurokinin-1 receptor antagonism in the central and medial but not basolateral nuclei of the amygdala in male Wistar rats. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 77, p. 146-154, . (12/22681-7)
DE OLIVEIRA, RITHIELE CRISTINA; DE OLIVEIRA, RICARDO; FALCONI-SOBRINHO, LUIZ LUCIANO; BIAGIONI, AUDREY FRANCESCHI; ALMADA, RAFAEL CARVALHO; DOS ANJOS-GARCIA, TAYLLON; BAZAGLIA-DE-SOUSA, GUILHERME; KHAN, ASMAT ULLAH; COIMBRA, NORBERTO CYSNE. Neurotoxic lesions of the pedunculopontine tegmental nucleus impair the elaboration of postictal antinociception. Physiology & Behavior, v. 194, p. 162-169, . (09/00668-6, 08/08955-1, 13/10984-8, 11/09850-1, 14/10742-7, 12/22681-7)

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