Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats

Chlorpyrifos (CPF) is a widely used insecticides which has been shown to al ter brain cell development. The current project was conducted to determine whether there are persistent behavioral effects of early [1 mg/kg/day postn atal days (PNDs) 1-4] or late (5 mg/kg/day PNDs 11-14) postnatal CPF exposu re in rats. We tested spontaneous alternation in a T-maze, locomotor activi ty in the Figure-8 apparatus and learning in the 16-arm radial maze, throug hout adolescence and into adulthood. Exposure during either neonatal period elicited significant long-term effects on cognitive behavior. In the radia l-arm maze, as has been seen previously, control male performed more accura tely than control females. Early postnatal CPF exposure reversed this effec t. With exposure on PNDs 1-4, females in the CPF group showed a reduction i n working and reference memory errors in the radial maze, reducing their er ror rate to that seen in control males; in contrast, CPF-exposed males exhi bited an increased in errors during the initial stages of training. When an imals were exposed on PNDs 11-14 and then tested in adolescence and adultho od, males showed a significant slowing of response latency in the T-maze an d the rate of habituation in the Figure-8 apparatus was slowed in both sexe s. When females were challenged acutely with the muscarinic antagonist, sco polamine, they did not show reference memory impairment, whereas controls d id;, these results suggest that adaptations occur after CPF exposure that l ead to loss of muscarinic cholinergic control of reference memory. No such changes were seen with a nicotinic cholinergic antagonist (mecamylamine). T hese results indicate that early neonatal exposure to CPF induces long-term changes in cognitive performance that, in keeping with the neurochemical c hanges seen previously, are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute ch allenges, thus uncovering the adaptive mechanisms that maintain basal perfo rmance. (C) 2001 Elsevier Science BY All rights reserved.