Development of Behavioral Tolerance to Organophosphates II: Physiological Aspects(Ontwikkeling van Gedragstolerantie voor Organofosfaten II: Neurofysiologische Aspecten)

摘要

In a recent study (9) it was found in rats that chronic treatment with theirreversible cholinesterase inhibitors diisopropylfluor-phosphate (DFP) or soman led to behavioral tolerance in the case of DFP, but not in the case of soman. Biochemically, no explanation was found for the difference between these two inhibitors. Notably, chronic administration of each of these inhibitors did not affect the availability of the nicotinic receptors at the motor endplate, in spite of very low cholinesterase activity. In an attempt to explain the different effects of these inhibitors, a neurophysiological approach seemed appropriate. The spontaneous quantal release of acetylcholine from diaphragm muscles in vitro from animals chronically treated with each inhibitor showed a similar trend; compared with controls, the miniature endplate potential (MEPP) frequency was decreased, which was significant for DFP, and the MEPP amplitude was increased, which was significant for soman. Neuromuscular function of muscle strips obtained from both DFP or soman-treated animals appeared significantly more sensitive to additional inhibitor added in vitro. This could simply be explained by the high pre-existing level of cholinesterase inhibition, but seems in contrast with the phenomenon of tolerance.