Preventive and antipsychotic effects of cannabidiol in an animal model of schizophrenia: the SHR strain

• Grant number: 17/06048-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2017
• Effective date (End): December 31, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Vanessa Costhek Abílio
• Grantee: Alessandra Cabral
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Schizophrenia is a high prevalence psychiatric disorder whose pharmacological treatment is associated with significant side effects and high rates treatment resistance. Therefore, investigating new therapeutic and preventive strategies for schizophrenia is paramount. Recently, we showed that treatment with cannabidiol (CBD) from 30 to 60 post-natal days prevented the emergence of behavioral abnormalities that model positive and cognitive symptoms of schizophrenia in the model of the SHR strain. These data suggest the use of CBD in the prevention of this disorder. In addition, acute antipsychotic effects of CBD were verified on some, but not all, behavioral changes of the SHR strain. Aim: Since the potential deleterious effects of a preventive treatment in individuals at risk for schizophrenia increase the lower the age of these individuals, the first aim of this project is to evaluate the preventive effects of treatment with later initiated CBD 45 to 75 days of life) on the behavioral changes presented by adult animals of the SHR strain. As a second aim, it will be evaluated whether the antipsychotic potential of CBD is increased when its administration is chronically in adult SHR animals. It will also be evaluated if this antipsychotic effect is long-lasting. Methods: Wistar and SHR rats will be used. To evaluate the preventive effects of CBD, rats will be treated from days 45 to 75 after birth at doses of 0.25, 0.5 or 2.5 mg / kg. The following behavioral assessments will be performed from 90 days of age: locomotion (its increase modulates the positive symptoms of schizophrenia), social interaction (its decrease modulates negative symptoms), pre-pulse inhibition of startle (deficits are characteristic in schizophrenia and indicate sensory-motor filter loss), contextual fear conditioning (deficits indicate losses in the processing of emotional information).To evaluate the antipsychotic effects of CBD, the rats will be treated from days 90 to 120 after birth at the same doses. The behavioral assessments described above will be performed immediately after the end of treatment and 30 days later. (AU)