Assessing anxiety and painful hypersensitivity as comorbidities associated with Epilepsy: effects of cannabidiol treatment and the role of CB1, TRPV1 and 5-HT1A receptors

• Grant number: 21/13622-6
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): August 01, 2022
• Effective date (End): December 29, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Norberto Cysne Coimbra
• Grantee: Willian Lazarini Lopes
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Patients with Epilepsies frequently develop neuropsychiatric comorbidities associated with epileptic seizures. Amongst the most common we can highlight the anxiety and alterations in the nociception, like painful hypersensitivity. The present study aims to characterize alterations inanxiety-like and nociceptive behaviors in a strain of rats genetically susceptible to Epilepsy (WistarAudiogenic Rat - WAR) and characterize the effects of cannabidiol (CBD) administration on these comorbidities, as well as the role of CB1, TRPV1, and 5-HT1A receptors located in the dorsal periaqueductal gray matter (dPAG) on CBD effects. Anxiety-like behaviors will be assessed in the openfield, light dark box, and elevated plus maze tests, while nociceptive behaviors will be assessed in the von Frey, acetone, and hot plate tests. The impact of acute and chronic epileptic seizures on anxiety-like and nociceptive behaviors will also be characterized. After that, the potential therapeutic effects of CBD on both anxiety and nociception will be investigated in animals with the comorbidity Epilepsy and anxiety. Additionally, CB1, TRPV1, and 5-HT1A receptors located in the PAG will be antagonized prior to CBD administration to assess the role of these receptors on anxiety-like and nociceptive behaviors on these comorbidities. Therefore, the results from the present project are extremely important to better characterize and understand the comorbidities anxiety and the painful hypersensitivity associated with Epilepsy and will provide important information about thetherapeutic effects of CBD and the role of CB1, TRPV1, and 5-HT1A receptors in neuropsychiatric comorbidities. (AU)