Fear and anxiety: role of the orexinergic system in the medial prefrontal cortex

• Grant number: 18/03898-1
• Support Opportunities: Research Grants - Young Investigators Grants
• Duration: March 01, 2019 - February 28, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Rafael Carvalho Almada
• Grantee: Rafael Carvalho Almada
• Host Institution: Faculdade de Ciências e Letras (FCL-ASSIS). Universidade Estadual Paulista (UNESP). Campus de Assis. Assis , SP, Brazil
• Associated researchers: Carsten T. Wotjak ; Newton Sabino Canteras ; Norberto Cysne Coimbra ; Telma Goncalves Carneiro Spera de Andrade
• Associated scholarship(s): 23/05880-0 - Fear and Anxiety: role of the orexinergic system in the medial prefrontal cortex, BP.TT; 23/00888-3 - Study of the role of orexinergic mechanisms in the dorsal hippocampus in contextual fear conditioning, BP.IC; 21/06557-3 - The role of Orexin-A in the medial prefrontal cortex in the expression of contextual conditioned fear, BP.IC; + associated scholarships 20/02724-0 - The role of the orexinergic system in the medial prefrontal cortex in the expression of contextual conditioned fear, BP.IC; 19/15757-6 - Fear and anxiety: role of the orexinergic system in the medial prefrontal cortex, BP.TT; 19/01713-7 - Fear and anxiety: role of orexinergic system in the prefrontal cortex, BP.JP - associated scholarships

Abstract

The ability to detect and predict threatening or stressful events is essential for our survival. Although recent studies have focused on mPFC as a fundamental structure in modulation of the emotionality, and the hypothalamus has also been implicated in the regulation of these processes, and the hypothalamic neuropeptide orexin (hypocretin) appears to be involved in the processing of states of fear and anxiety. In this context, it has been suggested that orexinergic neurons of the lateral hypothalamus (LH) projecting to the mPFC play an important role in the cognitive functions performed by the mPFC. However, the role of orexinergic mechanisms in the mPFC, especially the LH-mPFC pathway, during the organization of the behavioral responses associated with fear and anxiety is unknown. Therefore, using neurotracing, immunohistochemistry, neuropharmacology and optogenetic techniques associated with behavioral assays, the aims of the present study will be to investigate the role of orexinergic mechanisms in the prelimbic cortex (PL), sub-region of the mPFC, and the LH-PL pathways during the organization and expression of the defensive responses associated with fear and anxiety. Thus, our hypothesis is that orexinergic mechanisms, mainly via orexin type 1 (OX1R) receptors, are fundamental during the organization and expression of the behavioral responses associated with fear and anxiety. We expect that the present project could broaden our knowledge regarding the neurophysiology of fear and anxiety, as well as encourage the development of new drugs, especially new strategies for the treatment of psychiatric disorders. (AU)

Publicações científicas

(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)

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)

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)