Study of the modulation of afferent pathways to the rostral ventromedial medulla in depressive-like behavior and hyperalgesia induced by social stress in mice

• Grant number: 20/08363-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): June 01, 2021
• Effective date (End): May 31, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Felipe Villela Gomes
• Grantee: Marco Oreste Finocchio Pagliusi Junior
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/17597-3 - The impact of stress on the dopamine system depends on the state of the critical period of neuroplasticity: implications for depression and schizophrenia and for the study of new drug targets, AP.JP
• Associated scholarship(s): 23/01110-6 - Involvement of the projections from lateral habenula to RVM in the social defeat stress-induced behavioral impairments, BE.EP.PD

Abstract

Major Depressive Disorders (MDD) affect a significant portion of the world population (approximately 4.5%) and are diagnosed using criteria established by the Diagnostic and Statistical Manual of Mental Disorders. Although chronic pain is not among the symptoms of depression, epidemiological studies indicate a close association between MDD and chronic pain. Social Defeat Stress (SDS) model is currently being used to induce depressive-like behaviors and persistent hyperalgesia in mice. In this model, mice are exposed for 10 consecutive days to an aggressor physically more robust mouse stain, suffering brief periods of aggression followed by longer periods of visual and olfactory contact. It has also been shown that the SDS-induced chronic pain is similar to human fibromyalgia, a condition characterized by widespread chronic pain and closely related to depression. It is well known that pain starts from nociceptors activation followed by ascension - through specific neural pathways - of the electrical signal to higher levels of the CNS. These ascending pathways are modulated by several descending supraspinal pathways, serving as facilitatory and inhibitory endogenous system of pain. An important brain area associated with descending modulation of pain is the Rostral Ventromedial Medulla (RVM). This structure plays a key role in both facilitation and inhibition of pain, receiving projections from various brain areas such as periaqueductal gray matter, nucleus accumbens and anterior cingulate cortex. Not surprisingly, the above-mentioned areas are also related to depressive behavior. Based on this, the present project proposes to investigate, using a chemogenetic approach, the participation of the projection pathways to RVM in the depressive-like behavior and hyperalgesia induced by social defeat stress in mice. (AU)