Characterization of social behaviors and underlying neuronal activation and neurochemical alterations in an animal model of autism: evaluation of sexual dimorphisms and possible effects of cannabidiol.

• Grant number: 23/07422-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2024
• End date: April 30, 2027
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Vanessa Costhek Abílio
• Grantee: Lucas Teodoro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in the socio-communicative domain and the manifestation of restricted and repetitive behaviors and interests. ASD sociocommunicative deficits present sexual dimorphisms and are better masked in girls and women with the disorder. The main hypothesis that explains the sociocommunicative deficits in ASD is the theory of social motivation, which has now been expanded to also encompass social cognition and social skills. This theory suggests that, during childhood, some insult compromised the child's salience to social stimuli, altering the search for and taste for social stimuli. The main neural circuitry related to social motivation is the mesocorticolimbic pathway, but it is influenced by several other brain regions and neurotransmission systems that help to modulate social motivation. Among them are the oxytocinergic projections that project from the paraventricular nucleus of the hypothalamus to mesolimbic regions and the serotonergic projections from the dorsal raphe nucleus that project to mesocorticolimbic regions. In addition, the endocannabinoid system is capable of modulating various social behaviors. ASD presents alterations in these neurotransmission systems and understanding them helps to formulate new pharmacotherapeutic strategies. Therefore, the present work intends to: 1) evaluate different aspects of social behavior (tests of social interaction, social preference, social novelty and place-conditioned social preference) and neuronal activation (immunomarked by c-fos) at different ages (DPN 30 , 45, 60 and 90) in animals of both sexes submitted to the model of prenatal exposure to valproic acid (VPA); 2) to investigate neurochemical alterations in the monoaminergic and endocannabinoid systems at different ages (DPN 30, 45, 60 and 90) in animals of both sexes submitted to the model of prenatal exposure to valproic acid (VPA); 3) to investigate the effects of CBD treatment on behavioral, neuronal activation and neurochemical changes found.