Acute cannabidiol treatment reverses behavioral impairments induced by embryonic valproic acid exposure in male mice

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Pedrazzi, J. F. C. ; Sales, A. J. ; Ponciano, R. S. M. ; Ferreira, L. G. ; Ferreira, F. R. ; Campos, A. C. ; Hallak, J. E. C. ; Zuardi, A. W. ; Del Belad, E. A. ; Guimaraes, F. S. ; Crippa, J. A.

• Document type: Journal article
• Source: Pharmacology Biochemistry and Behavior; v. 247, p. 9-pg., 2024-12-17.

Abstract

Cannabidiol (CBD), the major non-psychotomimetic compound of the Cannabis sativa plant, has shown promising effects in addressing various symptoms associated with autism spectrum disorder (ASD). This neurodevelopmental disorder typically impacts cognitive, behavioral, social communication, and motor skills domains. However, effective treatments for the wide range of symptoms associated with the disorder are limited and may trigger undesirable effects. Embryonic exposure to valproic acid (VPA, 500 mg/kg at 12 degrees day embryonic age) in rodents is a consolidated environmental model for studying behavioral and molecular characteristics related to ASD. Therefore, this study aimed to evaluate whether acute CBD could reverse behavioral impairments in adult mice (eight weeks) exposed to VPA in the embryonic period in four distinct trials. In independent groups of animals, the following assays were conducted: I) Pre-Pulse Inhibition Test (PPI), II) Marble Burying, III) Social Interaction, IV) Actimeter Test, and V) Novel Object Recognition Test (NOR). In the PPI paradigm, mice exposed to VPA showed PPI impairment, and CBD (30 and 60 mg/kg) reversed this disruption. CBD (60 mg/kg) respectively decreased the number of buried marbles, improved social interaction time, but failed to reduce stereotyped-like movements in the VPA group. In NOR test CBD at both doses reversed the impairment in index of recognition induced in VPA group. These findings suggest that acute CBD administration can ameliorate behavioral impairments associated with ASD in a well-established animal model for studying this neurodevelopmental disorder. (AU)

• FAPESP's process: 22/05199-9 - Investigation of the therapeutic profile of cannabidiol in an animal model of Autism Spectrum Disorder
• Grantee: João Francisco Cordeiro Pedrazzi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants