CYCLODIENE RESISTANCE AT THE INSECT GABA RECEPTOR CHLORIDE CHANNEL COMPLEX CONFERS BROAD CROSS-RESISTANCE TO CONVULSANTS AND EXPERIMENTAL PHENYLPYRAZOLE INSECTICIDES

This study investigated the pharmacological profile of cyclodiene resi stance in Drosophila melanogaster and the mode of action of a phenylpy razole insecticide, JKU 0422. Toxicological studies were performed wit h a sucrose bait assay containing the synergist piperonyl butoxide. Th e Maryland strain of D. melanogaster was resistant to dieldrin, lindan e, picrotoxinin, TBPS, p-CN-TBOB, and JKU 0422. In contrast, this stra in was susceptible to cypermethrin and the avermectins MK-243, abamect in, and abamectin 8,9-oxide. Neurophysiological studies showed that bo th TBPS and JKU 0422 reversed the inhibitory action of GABA in central nerve preparations from susceptible D. melanogaster. However, the res ponse to these compounds was attenuated in nerve preparations from the resistant Maryland strain, which indicated that the resistance was ex pressed at the level of the nerve. Topical toxicity bioassays with JKU 0422 on susceptible (CSMA) and cyclodiene-resistant (LPP) strains of German cockroach revealed a resistance ratio of 553-fold for this comp ound. These studies demonstrate that cyclodiene resistance in D. melan ogaster confers broad cross resistance toward compounds thought to blo ck the GABA-gated chloride channel in a manner similar to the cyclodie nes. Moreover, the cross resistance extends to JKU 0422, and resistanc e to this compound is also present in a strain of cyclodiene-resistant German cockroach. These toxico logical results, along with the neurop hysiological studies, confirm that JKU 0422 has a mode of action that is similar to the cyclodienes and TBPS. These findings suggest that th e introduction and use of new chloride channel antagonists as insectic ides should be managed carefully in order to prevent the rapid develop ment of resistance in the field. (C) 1994 Wiley-Liss, Inc.