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Influence of the anterior cingulate cortex and involvement of hypothalamic NMDA and AMPA/kainite glutamatergic receptorsin the organization of the defensive behaviorand innate fear-induced antinociception elaborated by posterior hypothalamus

Grant number: 13/10984-8
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2013
Effective date (End): April 30, 2015
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Norberto Cysne Coimbra
Grantee:Luiz Luciano Falconi Sobrinho
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Eletrical and chemical stimulation of some mesencefalic strucutres, as dorsal periaqueductal grey matter, the deep layers of the superior colliculus and central nuclei of inferior colloculus elicite explosive defensive response, associated with fear and similar to those characterized to panic disorder in humans. However, when the stimulation are done into medial hypothalamus, the defensive response arecharacterized by a well elaborated escape. There are some evidence that the cingulate gyrus send projections to posterior hypothalamic nucleus, which the stimulation also is followed by escape and fear-induced antinociception. Medial and posterior hypothalamus, diencephalic strucutres related to envolviment with modulation of sympathetic division of the autonomic nervous system, are modulated by a tonic GABAergics pathways, which is critically recruited during the elaborations of defense responses. There are only a few works about mechanisms that underlie modulation of pain perception mediated cortical areas such as the anterior cingulate cortex (ACC). The aim of the presente work is to investigate the connections between the anterior cingulate cortex with posterior hypothalamic nuclei, and with the nuclei of the system of inhibition of endogenous pain such locus coeruleus and dorsal raphe nuclei, through a neuroanatomic study with microinjections of an iontophoretic neurotraçador of anterograde and retrograde, a biodextrana marked with Texas Red in the ACC, followed by Immunohistochemical methods for the detection and the type glutamate receptors NMDA e AMPA/Kainate into posterior hypothalamus. It will be also study the effect os neural inativation of cortical afferents described previously, by microinjection of lidocaina at 2% into-ACC, in order to investigate if these structures play some role modulating the fear-induced antinociception induced by posterior hypothalamus chemistry stiulation. Independents groups will be study in order to analise the effect os the pre-treatment into-postior hypothalamus with microinjections of LY235959, a NMDA receptor glutamatergic selective antagonist or NBQX, a AMPA e kainate receptor glutamatergic competitive antagonist, to evaluate the involviment of posteiror hypothalamus glutamatergic neurotransmitter during the organization of fear-induced antinociception induced by defensive reactions after bicuculline microinjections (40 ng / 200 nL), a GABAA receptor antagonist into-posteiror hypothalamus.

Scientific publications (7)
(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)
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, MAY 2019. Web of Science Citations: 1.
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, OCT 1 2018. Web of Science Citations: 1.
ULLAH, FARHAD; DOS ANJOS-GARCIA, TAYLLON; MENDES-GOMES, JOYCE; HIBRAHIM ELIAS-FILHO, DAOUD; FALCONI-SOBRINHO, LUIZ LUCIANO; DE FREITAS, RENATO LEONARDO; KHAN, ASMAT ULLAH; DE OLIVEIRA, RICARDO; COIMBRA, NORBERTO CYSNE. Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour. Behavioural Brain Research, v. 319, p. 135-147, FEB 15 2017. Web of Science Citations: 12.
DOS ANJOS-GARCIA, TAYLLON; ULLAH, FARHAD; FALCONI-SOBRINHO, LUIZ LUCIANO; COIMBRA, NORBERTO CYSNE. CB1 cannabinoid receptor-mediated anandamide signalling reduces the defensive behaviour evoked through GABA(A) receptor blockade in the dorsomedial division of the ventromedial hypothalamus. Neuropharmacology, v. 113, n. A, p. 156-166, FEB 2017. Web of Science Citations: 16.
FALCONI-SOBRINHO, LUIZ LUCIANO; DOS ANJOS-GARCIA, TAYLLON; ELIAS-FILHO, DAOUD HIBRAHIM; COIMBRA, NORBERTO CYSNE. Unravelling cortico-hypothalamic pathways regulating unconditioned fear-induced antinociception and defensive behaviours. Neuropharmacology, v. 113, n. A, p. 367-385, FEB 2017. Web of Science Citations: 15.
DE OLIVEIRA, RICARDO; DE OLIVEIRA, RITHIELE CRISTINA; FALCONI-SOBRINHO, LUIZ LUCIANO; SOARES, JR., RAIMUNDO DA SILVA; COIMBRA, NORBERTO CYSNE. 5-Hydroxytryptamine(2A/2C) receptors of nucleus raphe magnus and gigantocellularis/paragigantocellularis pars alpha reticular nuclei modulate the unconditioned fear-induced antinociception evoked by electrical stimulation of deep layers of the superior colliculus and dorsal periaqueductal grey matter. Behavioural Brain Research, v. 316, p. 294-304, JAN 1 2017. Web of Science Citations: 9.
BIAGIONI, AUDREY FRANCISCO; DOS ANJOS-GARCIA, TAYLLON; ULLAH, FARHAD; FISHER, ISAAC RENE; FALCONI-SOBRINHO, LUIZ LUCIANO; DE FREITAS, RENATO LEONARDO; FELIPPOTTI, TATIANA TOCCHINI; COIMBRA, NORBERTO CYSNE. Neuroethological validation of an experimental apparatus to evaluate oriented and non-oriented escape behaviours: Comparison between the polygonal arena with a burrow and the circular enclosure of an open-field test. Behavioural Brain Research, v. 298, n. B, p. 65-77, FEB 1 2016. Web of Science Citations: 15.

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