Sexual Dimorphisms and Behavioral and Neuroinflammatory Preventive Effects of Cannabidiol in an Animal Model of Schizophrenia Induced by Prenatal Immune Activation by Poly I:C

• Grant number: 24/17826-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Vanessa Costhek Abílio
• Grantee: Sara Avelino Beserra
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Schizophrenia is a chronic and heterogeneous psychiatric condition caused by neurodevelopmental alterations. Its course, symptom manifestation, and response to antipsychotics differ between men and women, evidencing sexual dimorphism. Even with the medications currently used, their effects do not fully cover all symptoms of the disorder and induce significant adverse effects, leading approximately half of the patients to discontinue treatment. Thus, the search for preventive strategies becomes crucial. Cannabidiol, a non-psychomimetic derivative of Cannabis sativa, exhibits anti-inflammatory activity and antipsychotic properties. Recently, our group has demonstrated its preventive potential for behavioral alterations observed in animal models for the study of schizophrenia. Therefore, the aim of this project is to further investigate the sexual dimorphisms associated with the behavioral and neuroinflammatory alterations induced by maternal immune activation (a neurodevelopmental model for schizophrenia) as well as the response to preventive treatment with cannabidiol. For this purpose, female mice of the C57BL/6J strain will be treated with poly I:C (10mg/kg) on the 12th day of gestation, and their offspring, both male and female animals, will undergo treatment with CBD (1mg/kg) during their periadolescence, between postnatal days 30 and 60. Behavioral (open field locomotor activity, prepulse inhibition test, social preference, and object recognition) and glial (quantification of astrocytes and activated microglia) assessments will be conducted during postnatal days 61-65 and 91-95.