A characterization of chemical kindling with the pesticide endosulfan

Abstract

In a companion article (see this issue), the proconvulsant properties of the pesticide endosulfan in electrical kindling of the amygdala are described. In the present report, an evaluation of the chemical kindling properties of endosulfan is presented. Repeated administration (3 times per week for a total of 21 doses) of endosulfan (5 and 10 mg/kg in corn oil, PO) was found to induce behavioral seizures in rats. Behavioral seizure development was most apparent in the high dose group (10 mg/kg). Heightened seizure responsiveness to a challenge dose was maintained following a two-week, drug-free period, arguing against cumulative toxicity as a mechanism for seizure induction. Electrical kindling induced by once daily stimulation of the amygdala began approximately 4 weeks after the final dose of endosulfan. In the absence of further dosing, a significant facilitation in the rate of kindling development was evident as a function of prior treatment with endosulfan. An enhancement in the rate of kindling was also evident in the low dose group (5 mg/kg) in the absence of clonic seizure development during dosing. A history of endosulfan treatment failed to affect threshold for inducing an afterdischarge (AD) and had equivocal effects on the development of AD with repeated stimulation. Pretreatment with a single high dose of endosulfan 2 weeks prior to electrical kindling was without effect on the development of the kindled response. Endosulfan has been reported to decrease binding of gamma-amino-butyric acid (GABA). Chemical kindling with endosulfan may result from the interaction of this pesticide with GABA-mediated neurotransmission in the central nervous system (CNS). Positive transfer to electrical kindling following a regimen of endosulfan dosing that produced only minor increases in the incidence of clonic seizures indicates that behavioral observations alone cannot predict the long term consequences of repeated exposure to pesticides.