PYRETHROID INSECTICIDES INDIRECTLY INHIBIT GABA-DEPENDENT CL-36- INFLUX IN SYNAPTONEUROSOMES FROM THE TROUT BRAIN

Rainbow trout (Oncorhynchus mykiss) are extremely sensitive to the neurotoxic activity of pyrethroid insecticides. One possible target for pyrethroids is the GABA(A) receptor of brain of the trout, the function of which can be tested by measurement of influx of Cl-36(-) into synaptoneurosomes, in response to the application of agonists. Gamma-aminobutyric acid produced a time- and concentration-dependent increase in influx of Cl-36(-) in synaptoneurosomes from the brain of the trout, which exhibited the pharmacology characteristic of a response mediated by activation of a GABA(A) receptor. Deltamethrin, (1R-alpha-S)-cis-cypermethrin and permethrin produced a dose-dependent increase in the basal uptake and a corresponding decrease in GABA-dependent influx, with a maximum inhibition of 70-82%. This effect of pyrethroid was stereospecific, of high potency and inhibited by tetrodotoxin (TTX) and t-butylbicyclophosphorothionate (TBPS). The sensitivity of the effect of the pyrethroid to TTX suggested an activation by pyrethroid of the voltage-dependent sodium channel. Veratridine, a sodium channel activator, elicited similar changes in the basal uptake of chloride, which were TTX-sensitive. Neither deltamethrin nor veratridine had a measurable effect on the efflux of Cl-36(-) from synaptoneurosomes. Thus, pyrethroid insecticides may interfere with the function of GABA(A) receptors indirectly through an interaction with the voltage-dependent sodium channel in the brain of the trout and consequently perturb chloride influx, possibly through a voltage-dependent chloride channel.