Study of the involvement of the P2X7 purinergic receptor in the dorsolateral periaqueductal gray in the modulation of conditioned emotional response to context: participation of the glutamate and nitric oxide pathway

• Grant number: 23/16556-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2024
• End date: December 31, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Leonardo Resstel Barbosa Moraes
• Grantee: Letícia Barros dos Santos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The dorsolateral periaqueductal gray substance (SCP-dl) is a mesencephalic structure associated with the expression of aversive behaviors. It expresses purinergic receptors called P2, activated by adenosine triphosphate (ATP). This family is divided into P2X and P2Y receptors, respectively increasing and decreasing the release of other neurotransmitters, such as glutamate. Among the P2X receptors, P2X7 stands out for having characteristics that differentiate it from the others, and it is also linked to pathologies of the nervous system associated with stress. Studies indicate that the activation of P2X7 receptors induces defensive behaviors, such as conditioned emotional response (CER). CER is characterized by freezing behavior and increased autonomic activity in context-conditioned fear (CCF). The glutamatergic system in SCP-dl is capable of inducing the synthesis of nitric oxide (NO) through the activation of NMDA receptors, and these systems are involved in defensive behaviors. Considering that glutamate and NO elicit defensive responses in SCP-dl in CCF and are influenced by P2X7 receptors, this project proposes to investigate the participation of the purinergic system, especially P2X7 receptors, in modulating CER associated with CCF and its interaction with the NMDA/NO pathway.Therefore, our hypothesis is that the activation of P2X7 receptors present in SCP-dl participates in the expression of CER, and that this response occurs with the involvement of the NMDA/NO/sGC receptor pathway.