SEIZURE THRESHOLDS IN KINDLED ANIMALS ARE REDUCED BY THE PESTICIDES LINDANE AND ENDOSULFAN

Lindane and endosulfan are chlorinated hydrocarbon pesticides that bind to the gamma-aminobutyric-acid(A) (GABA(A)) receptor ionophore complex. We have previously demonstrated development of a persistent predisposition to the seizure-inducing properties of these pesticides following repeated administration of initially subconvulsive doses. A subsequent facilitation of electrical kindling development indicated that a chemical kindling mechanism may contribute to this enhanced sensitivity. We tested the bidirectionality of kindling transfer induced by chemical and electrical means by comparing the convulsive thresholds of lindane and endosulfan in electrically kindled and nonkindled animals. Amygdala kindled, implanted/nonstimulated, and nonimplanted controls were administered 0, 5, 10, or 20 mg/kg of lindane or endosulfan in corn oil by gavage, anti each animal's behavior was scored for the presence of myoclonic jerks (MCJ) and clonic seizures. Dose-related increases ill the number of animals displaying convulsions in response to both of these pesticides were observed. The dose of lindane (4.5 mg/kg) and endosulfan (4.3 mg/kg) producing MCJs in 50% of the animals (ED(50)) was reduced by more than 60% in kindled animals relative to controls. A second experiment evaluated the generalized seizure threshold in previously kindled animals treated with low doses of endosulfan (0, 2.5, and 5 mg/kg, po by gavage). Endosulfan reduced the intensity of electrical stimulation required to evoke seizures in amygdala kindled animals. These data indicate that these chlorinated hydrocarbon insecticides reduce seizure thresholds in amygdala-kindled animals with acute administration, and together with previous findings (see ref. 20) demonstrate bidirectional transfer between chemical and electrical kindling. A reduction in afterdischarge threshold in limbic structures may be one mechanism whereby repeated dosing with lindane and endosulfan promotes the development of chemical kindling.