Chlorpyrifos releases norepinephrine from adult and neonatal rat brain synaptosomes

Exposure of developing animals to apparently subtoxic doses of chlorpyrifos (CPF) during a critical period of synaptogenesis has been shown to affect catecholaminergic synaptic development and neuronal activity separably from its inhibition of cholinesterase. We used rat brain synaptosome preparatio ns to examine whether CPF has a direct effect on the release of norepinephr ine (NE). Synaptosomes were preloaded with [H-3]NE in the absence of CPF an d were then exposed to the compound during subsequent neurotransmitter rele ase. There was a robust increase in release at 50 mu g/ml of CPF. The effec t was not mediated through cholinergic receptors, as neither atropine nor m ecamylamine interfered with the actions of CPF. Enhanced NE release was see n in synaptosomes derived from neonatal rat brain as well as adult rat brai n, albeit with a smaller effect in neonates. Our results suggest that CPF i nteracts directly with presynaptic nerve terminals to influence neurotransm itter release; in the context of the immature brain, these effects can alte r synaptic development through the trophic actions of catecholamines. (C) 1 999 Elsevier Science B.V. All rights reserved.