Behavioural and neuroendocrine effects of developmental exposure to a common organophosphate insecticide in two mouse strains: relevance for vulnerability to human neurodevelopment disorders.

Chlorpyrifos (CPF) is the most largely used organophosphate insecticide worldwide. Epidemiological studies have indicated that assumption of CPF by diet and indoor exposure at environmentally relevant doses affects behaviour and brain maturation in exposed children. We found that developmental exposure of the out bred CD1 mouse strain to low dose of CPF altered neonatal behaviour patterns, adult social responses and neuroendocrine markers in a sex-dimorphic fashion. In the present study the prenatal treatment schedule used for CD1 mice was applied to the inbred BTBR T+tf/J mouse strain, a validated model of autism-spectrum disorders. The etiology of autism is still obscure but it has become increasingly clear that both defective genes and environmental factors (including chemicals) concur to the pathogenesis of this clinical heterogeneous condition. BTBR mice exhibit an abnormal immune responses that may also contribute to a proper vulnerability to environmental insults. Moreover while the BTBR mouse has been shown to exhibit behavioural patterns thought to be relevant to the core domains of ASD, it is unknown whether these behaviour, relevant to ASD, can be further exacerbated by the effects of environmental insults, such as chlorpyrifos exposure. Pregnant BTBR mice were orally administered on gestational days 14-17 with either vehicle or CPF at a dose of 6 mg/kg/bw. Offspring of both sexes underwent neonatal assessment of sensorimotor milestones and ultrasound emission, and social investigation and/or courtship behaviour were investigated at adulthood. Our findings evidenced significant effects of CPF on neonatal behaviours and ultrasound emission with a different pattern of effects between CD1 and BTBR mice. BTBR-CPF males showed an abnormal courtship behaviour pattern of the receptive female, an effect not found in the CD1 males. Analysis of mRNA expression of oxytocin, vasopressin and steroid receptors in hypothalamus and amygdala evidenced important baseline differences between the two strains, which might be relevant for their different behavioural phenotypes and susceptibility to neurotoxicants' effects.