Pyrethroid insecticides evoke neurotransmitter release from rabbit striatal slices

The effects of the synthetic pyrethroid insecticide fenvalerate ([R,S]-α-cyano-3-phenoxybenzyl[R,S]-2-(4-chlorophenyl)-3-methylbutyr te) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of [³H]dopamine and [³H]acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of [³H]dopamine and [³H]acetylcholine by fenvalerate was modulated by D₂ dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of [³H]norepinephrine or [³H]acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions.