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 snakes

• 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
• 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)

Scientific publications

(9)

(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)

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., 2023-01-17. (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)

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., 2022-07-01. (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., 2022-10-14. (17/11855-8, 13/10984-8, 19/05255-3, 20/15050-7)

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., 2023-03-10. (21/14198-3, 21/13622-6, 20/15050-7, 21/14073-6, 19/05957-8, 18/06877-5)

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., 2022-06-02. (17/11855-8, 07/01174-1, 20/15050-7, 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., 2022-09-20. (21/06473-4, 20/15050-7, 17/16443-0)

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., 2023-01-01. (20/15050-7, 07/01174-1, 12/03798-0)

DE PAULA RODRIGUES, BRUNO MANGILI; COIMBRA, NORBERTO CYSNE. CB1 receptor signalling mediates cannabidiol-induced panicolytic-like effects and defensive antinociception impairment in mice threatened by Bothrops jararaca lancehead pit vipers. JOURNAL OF PSYCHOPHARMACOLOGY, v. 36, n. 12, p. 13-pg., 2022-08-10. (12/03798-0, 17/11855-8, 20/15050-7)

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., 2022-01-13. (17/11855-8, 07/01174-1, 20/15050-7, 12/03798-0)