Neonatal chlorpyrifos exposure alters synaptic development and neuronal activity in cholinergic and catecholaminergic pathways

After routine home application of chlorpyrifos (CPF), infant and child expo sures can exceed acceptable levels. We treated neonatal rats daily on postn atal days (PN) 1-4 (1 mg/kg) or days 11-14 (5 mg/kg), treatments that evoke d no overt signs of toxicity. Effects on the development of cholinegic neur onal function were assessed using choline acetyltransferase (ChAT) activity and hemicholinium-3 (HC-3) binding as indices of synaptic proliferation an d synaptic activity, respectively. In the forebrain, early CPF treatment ca used a decrease in ChAT without affecting HC-3 binding; late treatment decr eased HC-3 binding without affecting ChAT. In the brainstem, early treatmen t had no effect on either parameter but late treatment decreased both ChAT and HC-3 binding. Effects of CPF were not limited to development of choline rgic synapses but also involved catecholamine pathways. For norepinephrine or dopamine, either early or late CPF treatment evoked an increase in synap tic activity (transmitter turnover). The cerebellum, a region with sparse c holinergic innervation, was affected the most. Effects on catecholamine sys tems were unrelated to the magnitude or temporal pattern of cholinesterase inhibition. Our results suggest that CPF exposure during the postnatal peri od of synaptogenesis elicits widespread disruption of cholinergic and catec holaminergic, pathways. As this is the period in which patterns of synaptic responsiveness is programmed by neural input, the period of developmental vulnerability to CPF is likely to extend into childhood. (C) 1999 Elsevier Science B.V. All rights reserved.