Characterization of Chemical Kindling with the Pesticide Endosulfan.

摘要

The present report evaluated the chemical kindling properties of endosulfan. Repeated administration (3X/wk for 21 doses) of endosulfan was found to induce behavioral seizures in rats. Low dosages (5 & 10 mg/kg in corn oil, po) that were without overt toxicity in the majority of animals upon acute administration, began to elicit signs of seizure (myoclonic jerks and clonic seizures) upon repetition. Heightened seizure responsiveness was maintained following a 2-week wash out period, arguing against cumulative toxicity as a mechanism for seizure induction. Electrical kindling induced by once daily stimulation of the amygdala beginning approximately 4 weeks after the final dose of endosulfan, and in excess of 2 weeks, after the challenge dose revealed a significant facilitation in kindling rate. Thus, prior treatment with endosulfan promoted the development of kindled seizures in the absence of further dosing. A history of endosulfan treatment failed to affect threshold for inducing an afterdischarge (AD), but equivocal effects upon the development of AD. Pretreatment with a single high dose of endosulfan 2 weeks prior to electrical kindling was without effect upon development of the kindled response. Chemical kindling with endosulfan may result from the interaction of this pesticide with GABA-mediated neurotransmission in the central nervous system.