Exploring dopaminergic alterations and sociability in an animal model of autism

• Grant number: 23/14964-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 20, 2024
• End date: February 19, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Felipe Villela Gomes
• Grantee: Adriana de Jesus de Souza
• Supervisor: Jordi Bonaventura
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Universitat de Barcelona (UB), Spain
• Associated to the scholarship: 22/03345-8 - Neural circuits oscillatory activity during social interaction and novel object recognition task in an animal model for Autism, BP.DR

Abstract

Autism Spectrum Disorders (ASD) are a group of neurodevelopmental disorders that share behavioral alterations in the domains of social interaction, communication and repetitive or stereotyped behavior patterns. The idea that imbalances in dopaminergic neurotransmission in specific brain regions can lead to behavioral alterations similar to those observed in individuals with ASD has been extensively studied, especially in the mesocorticolimbic (MCL) circuit, which is involved in brain functions such as reward and motivation related behavior. Recent studies suggest a causal relationship between MCL dysfunction and ASD related social deficits. Individuals with ASD do not seem to attribute enough value to social interactions and prefer other environmental stimuli. This biased social behavior could be prompted by diminished prefrontal cortex (PFC) response to social stimuli, as well as structural and functional abnormalities of the MCL circuit found in individuals diagnosed with ASD. Additionally, previous findings from our group have already demonstrated an increase in the population of spontaneously active dopaminergic neurons in the ventral tegmental area (VTA) in an animal model of autism based on in utero exposure to valproic acid. Here, we aim to evaluate dopamine levels in VTA and nucleus accumbens (NAc) during a sociability test in mice exposed to valproic acid and evaluate whether the inhibition of dopaminergic neurotransmission within the mesocorticolimbic pathway (VTA-NAc) can alleviate the sociability deficits observed in mice exposed to valproic acid.