Effects of acute and chronic administration of DDVP (dichlorvos) on distribution of brain acetylcholine in rats.

DDVP (dichlorvos), an irreversible cholinesterase (ChE) inhibitor, was administered acutely and chronically to rats in order to investigate effects on the distribution of brain acetylcholine (ACh). In acutely treated animals (4 mg/kg, singly), cholinergic signs were evident and accompanied with a 100, 146, 113, and 61 per cent increase in total, free, labile-bound and stable-bound ACh content of the brain, respectively, and a 66 per cent decrease in acetylcholinesterase (AChE) activity 20 min after injection. In no animals treated chronically with a low dose (0.2 mg/kg/day for 9 or 90 days, or 1 mg/kg/day for 9 or 30 days), any overt sign was shown during the experimental period, and the stable-bound ACh content of the brain was not altered. In the group given 0.2 mg/kg for 90 days and that given 1.0 mg/kg for 9 or 30 days, free ACh content increased slightly but significantly, and AChE activity decreased to 58 per cent. Total ACh content and labile-bound ACh content increased only in a group given 1 mg/kg of DDVP for 30 days. These results suggest that acute, as well as chronic, exposure to organophosphate may induce alteration in mobilization and storage of ACh in the central cholinergic nerves.