Comparative Neurochemical Effects of Repeated Methyl Parathion or Chlorpyrifos Exposures in Neonatal and Adult Rats

Abstract

Several studies have reported higher sensitivity based on lethality in young animals compared to adults following acute exposure to organophosphorus insecticides (OPs). We propose that age-related differences in sensitivity to OPs may differ qualitatively and quantitatively with different OPs and varying exposure conditions (e.g., high vs. low dose, acute vs. repeated). To test this hypothesis, we treated neonatal (7 days of age) and adult (90 days of age) rats with either methyl parathion (MPS) or chlorpyrifos (CPF) daily for 14 days and measured neurochemical endpoints {cholinesterase (ChE) inhibition, total muscarinic receptor ([3H]quinuclidinyl benzilate, QNB) and muscarinic M2 subtype-preferential ([3H]AF-DX 384) binding} in frontal cortex and striatum at timepoints both during (1 day after the 7th and 14th dose) and after (8 days after the 14th dose) exposures. Repeated CPF exposures were associated with relatively similar degrees of ChE inhibition between the age groups during dosing but more extensive inhibition was noted in adults after termination of exposures. Relatively similar changes in muscarinic receptor binding were also noted between age groups following CPF exposures. Moreover, the degree of muscarinic receptor binding reduction relative to ChE inhibition appeared similar in both age groups following CPF exposures. In contrast, ChE activity and muscarinic receptor binding were generally more reduced in neonatal relative to adult brain regions following repeated MPS exposures. Furthermore, the relationship between the degree of ChE inhibition and the reduction in cortical muscarinic receptor binding appeared different between the age groups, i.e., more extensive reduction was noted in neonates compared to adults with a given level of ChE inhibition. We conclude that OP-selective differences in in vivo ChE sensitivity, differential rates of enzyme recovery following inhibition, and age-dependent differences in muscarinic receptor adaptations can all influence the nature of age-related susceptibility to OPs.