Developmental and social deficits and enhanced sensitivity to prenatal chlorpyrifos in PON1^-/- mouse pups and adults

The levels and activity of the enzyme paraoxonase 1 affect the vulnerability to the teratogenic effects of organophosphate pesticides. Mutant mice lacking the gene for paraoxonase1 (PON1^-/-) are more susceptible to the toxic effects of chlorpyrifos, and were hypothesized to be more vulnerable to social behavior deficits induced by exposure to chlorpyrifos during gestation. Three experiments were performed comparing PON1^-/- mice to PON1^+/+ mice born to dams treated with 0.5 mg/kg chlorpyrifos or cornoil vehicle on gestational days 12–15. Chlofpyrifos-exposed male PON1^-/- mouse pups had delayed development of reflexes in in the first experiment. In the second experiment, adult male and female PON1^-/- mice and the female PON1^+/+ mice all displayed lower social preference than the male vehicle-treated PON1^+/+ mice. The PON1^-/- mice and the female PON1^+/+ mice displayed lower social preference compared to the PON1^+/+ male mice. Male adult mice that had been exposed in utero to chlorpyrifos showed less conditioned social preference regardless of genotype. In the third study, the delayed reflex development was replicated in male and female PON1^-/- mice, but chlorpyrifos did not augment this effect. Nest Odor Preference, a test of early social attachment to dam and siblings, was lower in PON1^-/- mouse pups compared to PON1^+/+ pups. This study shows for the first time that PON1^-/- mice have a behavioral phenotype that indicates impaired reflex development and social behavior. Chlorpyrifos exposure during gestation tended to augment some of these effects.