Pupariation in flies: A tool for monitoring effects of drugs, venoms, and other neurotoxic compounds

Abstract

AbstractA complex Sarcophaga bullata pupariation assay was used to evaluate the neurotropic effects of several drugs, venoms, and insecticides. The assay consists of tests for (1) immediate effects on the intact larva, (2) effects on ligated (ie, isolated from the central nervous system) larval abdomens, (3) morphogenetic effects on the puparium, and (4) effects on stereotyped pupariation behavior. The latter are monitored barographically by recording changes in hemocoelic pressure. Of 62 compounds screened, 18 showed morphogenetic activity at a threshold dose of 5 μg or less, 11 at a dose of 50 μg, four at a dose of 100 μg, and 29 showed no morphogenetic activity. From a comparison of the putative pharmacological actions of the tested compounds with their morphogenetic effects, certain generalizations can be made: Agents that paralyze neuromuscular systems at the peripheral level (eg, tetrodotoxin), or suppress or modify basic motor patterns centrally (eg, veratrine sulphate), cause retention of larval morphological characters in the puparium. Compounds that stimulate convulsive contractions of segmental musculature (mostly cholinergic drugs like eserine sulphate, nicotine, organophosphate insecticides) cause retention of larval segmentation on longitudinally contracted puparia. Five compounds (venom of the scorpion, Leirus quinquestriatus, pyrethrins, protoveratrine A, and kainic and quisqualic acids) stimulate musculature of the denervated abdomen. Barographic monitoring of changes in pupariation behavior appears to be a most sensitive and informative test. It reveals great differences in the ways in which compounds producing seemingly identical morphogenetic effects affect and modify behavior, thus making pharmacological classification more accurate.