Vertebrate cyclodiene insecticide resistance: role of gamma-aminobutyric acid and diazepam binding sites.

Certain populations of the mosquitofish (Gambusia affinis) are highly resistant to cyclodiene and cyclodiene-type insecticides that competitively interact with the picrotoxinin binding site of the gamma-aminobutyric acid (GABA) receptor-ionophore complex in the central nervous system. Resistance involves a reduction in affinity of the picrotoxinin binding site. The present study reports that GABA receptor binding is increased in resistant brain membranes compared to membranes from susceptible fish at concentrations of free radioligand above 0.2 microM. The increase appears to be due to a greater number of binding sites (Bmax) in the resistant population. Diazepam binding affinity (Kd) and Bmax were not different in membranes from resistant fish compared to those from susceptible fish. Up-regulation of GABA binding sites in the resistant fish population may compensate for a possible reduction of GABAergic transmission caused by chronic environmental exposure to cyclodiene insecticides. However, a lack of cross-resistance to bicuculline (a competitive GABA antagonist) indicates that an increase in GABA sites is not a mechanism of cyclodiene resistance.