Study of nigro-tectal GABAergic pathways activity during the elaboration of defensive behaviour: role of endocannabinoid mediated neuromodulation in the caudatum putamen of the GABAergic disinhibitory neostriatum-nigral inhibitory nigro-collicular pathways

• Grant number: 15/10313-1
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): September 01, 2015
• Effective date (End): August 31, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Norberto Cysne Coimbra
• Grantee: Juliana Almeida da Silva
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Many studies suggest the midbrain tectum as responsible for the control of defensive responses elicited during situations of imminent danger. The periaqueductal grey matter, the deep layers of superior colliculus (dlSC) and the inferior colliculus have been considered important structures for the organisation of innate fear and defensive behaviour. GABAergic neurons of the the substantia nigra, pars reticulata (SNpr), connected to the dlSC and the reticular formation receive convergent synaptic inputs from the globus pallidus and neostriatum and modulate defense responses, for example, organized by PAG dorsal columns. The ventral midbrain has also cannabinoid CB1-type receptors that may contribute to the modulation of defensive behaviour and both Cannabis sativa-derived drugs, such as canabidiol, and endogenous cannabinoids, such as anandamide, act not only CB1/CB2 receptors, but also on vanilloid type 1 ion channels (TRPV1), which can be recruited for the modulation of the expression of defensive behaviours. Therefore, the purpose of this work is to study the role of endocannabinoid system and endovaniloid-mediated mechanisms of the neostriatum, a subtelencephalic structure rich in GABAergic neurons, involved in neostriatum-nigral projection, in the modulation of defensive behaviour that has been related to innate fear and panic attacks that seems to be under GABAergic tonic inhibition through the activity of nigro-tectal inhibitory neural pathways. Thus, the effects of microinjection of either cobalt chloride, NMDA and TRPV1 antagonists/agonists, of the effect of CB1cannabinoid receptors antagonists in neostriatum on the elaboration of the defensive behaviour elicited the dorsal midbrain (dlSC) chemical stimulation with a selective GABA-A receptor antagonist. (AU)

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; 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, NOV 2019. (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)

DE FREITAS, RENATO LEONARDO; MEDEIROS, PRISCILA; DA SILVA, JULIANA ALMEIDA; DE OLIVEIRA, RITHIELE CRISTINA; DE OLIVEIRA, RICARDO; ULLAH, FARHAD; KHAN, ASMAT ULLAH; COIMBRA, NORBERTO CYSNE. THE mu(1)-OPIOID RECEPTOR AND 5-HT2A- AND 5HT(2C)-SEROTONERGIC RECEPTORS OF THE LOCUS COERULEUS ARE CRITICAL IN ELABORATING HYPOALGESIA INDUCED BY TONIC AND TONIC-CLONIC SEIZURES. Neuroscience, v. 336, p. 133-145, NOV 12 2016. (14/11869-0, 09/02458-9, 11/09850-1, 12/25167-2, 13/12916-0, 09/00668-6, 09/17258-5, 15/10313-1)

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, OCT 2017. (14/11869-0, 09/02458-9, 14/10742-7, 17/11855-8, 12/03798-0, 09/54014-7, 10/15140-4, 13/12916-0, 09/17258-5, 07/01174-1, 15/10313-1, 12/22681-7)

CALVO, FABRICIO; LOBAO-SOARES, BRUNO; DE FREITAS, RENATO LEONARDO; PASCHOALIN-MAURIN, TATIANA; DOS ANJOS-GARCIA, TAYLLON; MEDEIROS, PRISCILA; DA SILVA, JULIANA ALMEIDA; LOVICK, THELMA ANDERSON; COIMBRA, NORBERTO CYSNE. The endogenous opioid system modulates defensive behavior evoked by Crotalus durissus terrificus: Panicolytic-like effect of intracollicular non-selective opioid receptors blockade. JOURNAL OF PSYCHOPHARMACOLOGY, v. 33, n. 1, p. 51-61, JAN 2019. (14/11869-0, 07/01174-1, 15/10313-1, 17/11855-8, 09/02458-9, 12/03798-0, 13/12916-0, 12/25167-2)

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. (09/02458-9, 13/10984-8, 17/11855-8, 17/13560-5, 12/25167-2, 12/03798-0, 07/01174-1, 15/10313-1, 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, JUN 2020. (19/01713-7, 17/11855-8, 15/10313-1, 09/02458-9, 07/01174-1, 12/03798-0, 18/03898-1, 12/22681-7)

DA SILVA, JULIANA ALMEIDA; ALMADA, RAFAEL CARVALHO; DE FIGUEIREDO, REBECA MACHADO; COIMBRA, NORBERTO CYSNE. Blockade of synaptic activity in the neostriatum and activation of striatal efferent pathways produce opposite effects on panic attack-like defensive behaviours evoked by GABAergic disinhibition in the deep layers of the superior colliculus. Physiology & Behavior, v. 196, p. 104-111, NOV 1 2018. (07/01174-1, 15/10313-1, 09/02458-9, 12/03798-0, 12/22681-7, 09/54014-7)