Neurotoxic insecticides inhibit GABA-dependent chloride uptake by mouse brain vesicles

The neurotoxic insecticides endrin, dieldrin, aldrin, lindane (gamma-1,2,3,4,5,6-hexachlorocyclohexane) and deltamethrin inhibited gamma-aminobutyric acid-dependent 36Cl- uptake by mouse brain vesicles. Of the insecticides examined, the chlorinated cyclodienes endrin and dieldrin were the most potent, producing 50% inhibition at 2.8 and 13.9 microM, respectively. Lindane and deltamethrin were less effective, and with deltamethrin the effect was incompletely stereospecific. These results demonstrate the disruption of gamma-aminobutyric acid receptor-chloride ionophore function in mammalian brain by neurotoxic insecticides and provide evidence that this complex is the principal site of cyclodiene action.