Age-related effects of chlorpyrifos on acetylcholine release in rat brain

Chlorpyrifos (CPF) is art organophosphorus insecticide that elicits toxicit y through inhibition of acetylcholinesterase (AChE). Young animals ar-e mar kedly more sensitive than adults to the acute toxicity of CPF: We evaluated acetylcholine (ACh) release and its muscarinic receptor-mediated regulatio n (i.e. muscarinic autoreceptor function, MAF) during maturation as a possi ble contributing factor to age-related differences in sensitivity, Cortical and striatal slices were prelabeled with [H-3]choline chloride, superfused in the presence or absence of the anticholinesterase physostigmine (PHY: 2 0 muM) and stimulated twice (S1 and S2) with a high concentration of potass ium chloride (20 mM). Depolarization-stimulated ACh release (DSAR) was lowe st in neonatal, intermediate in juvenile and markedly higher in adult tissu es. MAF was not detectable in tissues Slam neonatal rats but was present in juvenile and adult tissues. ACh release and MAF were studied at 4, 24 and 96 h following oral exposure to CPF (0, 0.5 or 1 x LD10). in general, 40-60 % and 80-90% maximal AChE inhibition followed exposure to the respective 0. 5 and 1 x LD10 dosages. DSAR was decreased in neonatal cortex I day after L D10 exposure but increased in juvenile striatum I day after LD10 treatment. In adults, DSAR was reduced at 4 and 24 h after exposure, but increased 96 h after CPF exposure. In juveniles, MAF was reduced in both brain regions at 24 h after 0.5LD(10) exposure and at 24 and 96h after LD10 exposure in c ortex. A later I-eduction in MAF was noted in adult tissues (i.e. only at 9 6 h after LD10 treatment). Together; the results suggest that ACh release d ynamics in brain vary markedly during postnatal maturation and that acute C PF exposure can alter ACh release in an age-related manner The functional s tatus of presynaptic processes regulating neurotransmitter release may cont ribute to age-related neurotoxicity elicited by high-dose exposures to chlo rpyrifos. (C) 2001 Elsevier Science Inc. All rights reserved.