Development is especially sensitive to Chlorpyrifos (CPF) toxicity, associated with several neurodegenerative
and neurodevelopmental disorders where motor function dysfunction is a core symptom. Amongst the alternative molecular targets to cholinesterases inhibition, developmental CPF alters different components in the
most important neurotransmitter systems, although this depends on the exposure period. Exposure during the
late postnatal preweaning stage is the least studied by far. This period includes essential neurodevelopmental
processes and has an important translational meaning. The present study analyzed the influence of low doses of
CPF on this developmental window on locomotor activity and the state of the different neurotransmitter systems
by pharmacological challenges. Brain gene expression and microbiome modulation following CPF were also
analyzed. CPF exposure long-term increased spontaneous vertical activity, female's activity following acute
stress, hyposensitized the cholinergic system and hypersensitized the GABAergic system, up-regulated both
muscarinic 2 receptor and GABA-A-α2 receptor subunit in the dorsal striatum and the frontal cortex, respectively
and induced gut microbiota dysbiosis at both genus and species levels. The present study supports alternative
molecular targets than the ChEs following late postnatal, preweaning exposure to low doses of CPF, focusing on
both cholinergic and GABAergic systems and the gut microbiome as an important factor.
