Autism spectrum disorder (ASD) is a complex neurodevelopmental pathology characterized by altered verbalizations, reduced social interaction behavior, and stereotypies. Environmental factors have been associated with
its development. Some researchers have focused on pesticide exposure. Chlorpyrifos (CPF) is the most used
Organophosphate. Previous developmental studies with CPF showed decreased, enhanced or no effect on social
outcomes eminently in mice. The study of CPF exposure during preweaning stages on social behavior is sparse in
mice and non-existent in rats. d stressors could be at the basis of ASD development, and around postnatal day 10
in the rat is equivalent to the human birthday in neurodevelopmental terms. We explored the effects of exposure
to low doses (1mg/kg/mL/day) of CPF during this stage regarding: sociability, dominance gut microbiome and
plasma metabolomic profile, since alterations in these systems have also been linked to ASD. There was a modest
influence of CPF on social behavior in adulthood, with null effects during adolescence. Dominance and hierarchical status were not affected by exposure. Dominance status explained the significant reduction in reaction
to social novelty observed on the sociability test. CPF induced a significant gut microbiome dysbiosis and
triggered a hyperlipidemic, hypoglycemic/hypogluconeogenesis and a general altered cell energy production in
females. These behavioral results in rats extend and complement previous studies with mice and show novel
influences on gut metagenomics and plasma lipid profile and metabolomics, but do not stablish a relation between the exposure to CPF and the ASD phenotype. The effects of dominance status on reaction to social novelty
have an important methodological meaning for future research on sociability.
