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Study of the role played by endocannabinoid and endovaniloid signalling in the pallidum on the activity of the neostriatum-pallido-nigral disinhibitory and nigro-tectal inhibitory pathways during the organization of innate fear of animals confronted to sn

Grant number:20/15050-7
Support Opportunities:Regular Research Grants
Start date: June 01, 2022
End date: May 31, 2024
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Norberto Cysne Coimbra
Grantee:Norberto Cysne Coimbra
Host Institution:Instituto de Neurociências e Comportamento (INEC). Ribeirão Preto , SP, Brazil
City of the host institution:Ribeirão Preto
Associated researchers:Rafael Carvalho Almada

Abstract

There is a great scientific interest in the search of the neuropsychopharmacological bases of fear- and panic-like behaviour. Several studies suggest the mesencephalic tectum (MT) as responsible for the control of defensive responses elaborated during threatening situations. The deep layers of the superior colliculus (dlSC) are considered relevant structures for the elaboration of innate fear and defensive behaviour. The substantia nigra, pars reticulata (SNpr), is known for its role in the modulation of the activity of the intermediate layers of the superior colliculus (ilSC) and dlSC and can work as a sensorial channel to tectal neurons responsible for the organization of defensive reactions in cranial mesencephalon. There is evidence that the neocortex send connexions to the neostriatum, which through globus pallidus is connected to the SNpr. The reticulate division of the substantia nigra in turn sends GABAergic connexions to the tectum. Outputs from ventromedial division of the SNpr are also connected to the CPu. The basal nuclei, particularly the globus pallidus and functionally related structures, such the SNpr, have elevated density of cannabinoid receptors type 1 (CB1) and TRPV1. In the globus pallidus, these receptors are situated presinapticaly, mainly in GABaergic neurons connected to the striatum. The present work aims to investigate the endogenous signaling of AEA and 2-AG, via CB1 and TRPV1 receptors of the globus pallidus during the organization of panic-like behaviour of rodents confronted with snakes of Bothrops genus, such as Bothrops jararaca, Bothrops alternatus e Bothrops moojeni. In addition, the morphology of the nigro-tectal pathway will be also studied focusing on the GABAergic neurons subtype connected to the dlSC. For that purpose, it will be studied the effect of microinjections of AM251, a CB1- receptor antagonist, URB597, a FAAH inhibitor, URB602, a 2-AG hydrolysis inhibitor, and the TRPV1 antagonist 6-hidroxi-capsaicin, in the globus pallidus, on the elaboration of the defensive behaviour by dorsal midbrain structures induced by dlSC GABAA receptor blockade in rats threatened by wild snakes. Finally, in a neuroanatomical approach, it will be investigated the morphologic characteristics of the GABAergic neurons connected to the dlSC. (AU)

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Scientific publications (17)
(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)
LAZARINI-LOPES, WILLIAN; SILVA-CARDOSO, GLEICE KELLI; CORTES DE OLIVEIRA, JOSE ANTONIO; CORREA PASSOS, LUIZ AUGUSTO; SALGADO, ANDREIA RUIS; RODRIGUES DEMOLIN, DANIELE MASSELLI; ANDRADE LEITE-PANISSI, CHRISTIE RAMOS; GARCIA-CAIRASCO, NORBERTO; COIMBRA, NORBERTO CYSNE. Inherited pain hypersensitivity and increased anxiety-like behaviors are associated with genetic epilepsy in Wistar Audiogenic Rats: Short- and long-term effects of acute and chronic seizures on nociception and anxiety. Epilepsy & Behavior, v. 141, p. 13-pg., . (21/14198-3, 21/13622-6, 20/15050-7, 21/14073-6, 19/05957-8, 18/06877-5)
FALCONI-SOBRINHO, LUIZ LUCIANO; DOS ANJOS-GARCIA, TAYLLON; HERNANDES, PALOMA MOLINA; RODRIGUES, BRUNO MANGILI DE PAULA; ALMADA, RAFAEL CARVALHO; COIMBRA, NORBERTO CYSNE. Unravelling the dorsal periaqueductal grey matter NMDA receptors relevance in the nitric oxide-mediated panic-like behaviour and defensive antinociception organised by the anterior hypothalamus of male mice. Psychopharmacology, v. N/A, p. 17-pg., . (17/22647-7, 12/22681-7, 17/11855-8, 07/01174-1, 19/01713-7, 18/03898-1, 13/10984-8, 20/15050-7, 12/03798-0)
SAMPAIO, M. F. S.; DE PAIVA, Y. B.; LOPES-SANTOS, L. E.; SANGUEDO, F. V. C.; NEVES, F. S.; PEREIRA, M. G.; COIMBRA, N. C.. Medicinal Cannabis and cannabinoids for the treatment of depression and anxiety: a literature review. Genetics and Molecular Research, v. 23, n. 1, p. 13-pg., . (20/15050-7)
MELO-THOMAS, LIANA; TACKEN, LARS; RICHTER, NICOLE; DE ALMEIDA, DAVINA; RAPOSO, CATARINA; DE MELO, SILVANA REGINA; THOMAS, UWE; DE PAIVA, YARA BEZERRA; MEDEIROS, PRISCILA; COIMBRA, NORBERTO CYSNE; et al. Lateralization in Hemiparkinsonian Rats Is Affected by either Deep Brain Stimulation or Glutamatergic Neurotransmission in the Inferior Colliculus. ENEURO, v. 9, n. 4, p. 19-pg., . (17/19799-0, 19/11448-9, 20/15050-7, 15/04194-0, 17/13560-5)
DE FIGUEIREDO, REBECA MACHADO; FALCONI-SOBRINHO, LUIZ LUCIANO; ANDRADE LEITE-PANISSI, CHRISTIE RAMOS; HUSTON, JOSEPH P.; MATTERN, CLAUDIA; DE CARVALHO, MILENE CRISTINA; COIMBRA, NORBERTO CYSNE. D-2-like receptor activation by intranasal dopamine attenuates fear responses induced by electrical stimulation of the dorsal periaqueductal grey matter, but fails to reduce aversion to pit vipers and T-maze performance. JOURNAL OF PSYCHOPHARMACOLOGY, v. 36, n. 11, p. 16-pg., . (17/11855-8, 13/10984-8, 19/05255-3, 20/15050-7)
OLIVEIRA, GABRIELA V. M.; SUZUKI, GABRIELA M. F.; SORIANO, RAFAEL F.; ALVES, LAIS V. DE CARVALHO; DE CARVALHO, MILLENA LANA C.; HERNANDES, PALOMA M.; WOTJAK, CARSTEN T.; COIMBRA, NORBERTO C.; ALMADA, RAFAEL C.. Differential modulation of contextual fear conditioning by orexin receptors in the dorsal hippocampus. Behavioural Brain Research, v. 501, p. 12-pg., . (23/00888-3, 18/03898-1, 19/01713-7, 20/15050-7, 21/06557-3, 21/14073-6, 24/01368-6)
FALCONI-SOBRINHO, LUIZ LUCIANO; FONSECA-RODRIGUES, DIANA; SILVA, ANA LAURA; DA SILVA, JOSIE RESENDE TORRES; COIMBRA, NORBERTO CYSNE; PINTO-RIBEIRO, FILIPA. Activation of NMDA Receptors in the Anterior Cingulate Cortex Enhances Anxiety-Induced Behaviour and Antinociception, and Contributes to the Modulation of Pain-Facilitatory Descending Pathways. EUROPEAN JOURNAL OF PAIN, v. 29, n. 6, p. 14-pg., . (21/13219-7, 17/11855-8, 07/01174-1, 12/03798-0, 20/15050-7, 19/05255-3, 21/14073-6)
SAMPAIO, MARIA DE FATIMA DOS SANTOS; DE PAIVA, YARA BEZERRA; SAMPAIO, TUANE BAZANELLA; PEREIRA, MESSIAS GONZAGA; COIMBRA, NORBERTO CYSNE. Therapeutic applicability of cannabidiol and other phytocannabinoids in epilepsy, multiple sclerosis and Parkinson's disease and in comorbidity with psychiatric disorders. BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY, v. 134, n. 5, p. 28-pg., . (14/11869-0, 20/15050-7)
FALCONI-SOBRINHO, LUIZ LUCIANO; DOS ANJOS-GARCIA, TAYLLON; REBELO, MACARIO AROSTI; HERNANDES, PALOMA MOLINA; ALMADA, RAFAEL CARVALHO; TANUS-SANTOS, JOSE EDUARDO; COIMBRA, NORBERTO CYSNE. The anterior cingulate cortex and its interface with the dorsal periaqueductal grey regulating nitric oxide-mediated panic-like behaviour and defensive antinociception. Neuropharmacology, v. 245, p. 17-pg., . (17/11855-8, 19/05255-3, 17/22647-7, 12/03798-0, 20/15050-7, 21/14073-6, 12/22681-7, 18/03898-1, 19/01713-7, 13/10984-8, 07/01174-1)
ALMADA, RAFAEL C.; FALCONI-SOBRINHO, LUIZ LUCIANO; DA SILVA, JULIANA A.; WOTJAK, CARSTEN T.; COIMBRA, NORBERTO C.. Augmented anandamide signalling in the substantia nigra pars reticulata mediates panicolytic-like effects in mice confronted by Crotalus durissus terrificus pit vipers. Psychopharmacology, v. N/A, p. 17-pg., . (17/11855-8, 07/01174-1, 20/15050-7, 12/03798-0)
SILVA, JULIANA ALMEIDA DA; ALMADA, RAFAEL CARVALHO; FALCONI-SOBRINHO, LUIZ LUCIANO; PIGATTO, GLAUCE REGINA; HERNANDES, PALOMA MOLINA; COIMBRA, NORBERTO CYSNE. Neostriatum neuronal TRPV1-signalling mediates striatal anandamide at high concentration facilitatory influence on neostriato-nigral dishinhibitory GABAergic connections. Brain Research Bulletin, v. 192, p. 14-pg., . (20/15050-7, 07/01174-1, 12/03798-0)
CARDOSO, FABRIZIO DOS SANTOS; SALEHPOUR, FARZAD; COIMBRA, NORBERTO CYSNE; GONZALEZ-LIMA, FRANCISCO; GOMES DA SILVA, SERGIO. Photobiomodulation for the treatment of neuroinflammation: A systematic review of controlled laboratory animal studies. FRONTIERS IN NEUROSCIENCE, v. 16, p. 13-pg., . (21/06473-4, 20/15050-7, 17/16443-0)
DOS ANJOS-GARCIA, TAYLLON; KANASHIRO, ALEXANDRE; DE CAMPOS, ALLINE CRISTINA; COIMBRA, NORBERTO CYSNE. Environmental Enrichment Facilitates Anxiety in Conflict-Based Tests but Inhibits Predator Threat-Induced Defensive Behaviour in Male Mice. NEUROPSYCHOBIOLOGY, v. N/A, p. 12-pg., . (17/11855-8, 07/01174-1, 20/15050-7, 12/03798-0)
SAMPAIO, M. F. S.; TRANCOSO, I.; COIMBRA, N. C.; PEREIRA, M. G.. Challenges and opportunities for therapeutic use of medical cannabis. Genetics and Molecular Research, v. 23, n. 1, p. 12-pg., . (20/15050-7)
RODRIGUES, BRUNO MANGILI DE PAULA; HERNANDES, PALOMA MOLINA; BALVEDI, RAFAEL CANALLE; ALVES, HIGOR FERREIRA MARTINS; DA SILVA, KAROLINE PAIVA; BICUDO, ROGRIO DE CAMPOS; EBERHARDT, MARCELO JUNG; POLETTO, FERNANDA; PAESE, KARINA; GUTERRES, SILVIA STANISCASKI; et al. Unravelling a potential therapeutic effect of polymeric lipid-core nanoencapsulated cannabidiol on anxiety-and panic-like behaviours elicited by Bothrops jararaca lancehead pit vipers. International Journal of Pharmaceutics, v. 679, p. 19-pg., . (12/03798-0, 17/11855-8, 24/01368-6, 20/15050-7)
OLIVEIRA, GABRIELA V. M.; HERNANDES, PALOMA M.; SANTOS, FABIO H. DOS; SOARES, VICTOR P. M. N.; FALCONI-SOBRINHO, LUIZ LUCIANO; COIMBRA, NORBERTO C.; WOTJAK, CARSTEN T.; ALMADA, RAFAEL CARVALHO. Orexin mechanisms in the prelimbic cortex modulate the expression of contextual conditioned fear. Psychopharmacology, v. N/A, p. 12-pg., . (21/06557-3, 20/02724-0, 19/05255-3, 20/15050-7, 21/14073-6, 19/15757-6, 18/03898-1, 19/01713-7, 13/10984-8)