Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats.
Chlorpyrifos (CPF) is a widely used insecticides which has been shown to alter brain cell development. The current project was conducted to determine whether there are persistent behavioral effects of early [1 mg/kg/day postnatal days (PNDs) 1-4] or late (5 mg/kg/day PNDs 11-14) postnatal CPF exposure in rats. We tested spontaneous alternation in a T-maze, locomotor activity in the Figure-8 apparatus and learning in the 16-arm radial maze, throughout adolescence and into adulthood. Exposure during either neonatal period elicited significant long-term effects on cognitive behavior. In the radial-arm maze, as has been seen previously, control male performed more accurately than control females. Early postnatal CPF exposure reversed this effect. With exposure on PNDs 1-4, females in the CPF group showed a reduction in working and reference memory errors in the radial maze, reducing their error rate to that seen in control males; in contrast, CPF-exposed males exhibited an increase in errors during the initial stages of training. When animals were exposed on PNDs 11-14 and then tested in adolescence and adulthood, males showed a significant slowing of response latency in the T-maze and the rate of habituation in the Figure-8 apparatus was slowed in both sexes. When females were challenged acutely with the muscarinic antagonist, scopolamine, they did not show reference memory impairment, whereas controls did; these results suggest that adaptations occur after CPF exposure that lead to loss of muscarinic cholinergic control of reference memory. No such changes were seen with a nicotinic cholinergic antagonist (mecamylamine). These results indicate that early neonatal exposure to CPF induces long-term changes in cognitive performance that, in keeping with the neurochemical changes seen previously, are distinctly gender-selective. Additional defects may be revealed by similar strategies that subject the animals to acute challenges, thus uncovering the adaptive mechanisms that maintain basal performance.
Levin
E D
ED
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA. edlevin@duke.edu
Addy
N
N
Nakajima
A
A
Christopher
N C
NC
Seidler
F J
FJ
Slotkin
T A
TA
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects*; D004390:Chlorpyrifos / Q000494:pharmacology*; D005260:Female; D007306:Insecticides / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology
D007306:Insecticides; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D012601:Scopolamine; D004390:Chlorpyrifos