On the development of behavioral tolerance to organophosphates. I: Behavioral and biochemical aspects.
The development of tolerance to organophosphates (OPs) was investigated by SC injections of saline and sublethal doses of DFP or soman three times per week or every other day for at least 4 weeks. Shuttlebox performance was tested 1 hr and 24 hr after the injections. Notwithstanding a progressive inhibition of AChE to very low values in various organs, shuttlebox performance was virtually normal 24 hr after the OP injections. However, whereas the performance decrements measured 1 h after the injection of DFP practically disappeared in the course of weeks, the decrements 1 hr after soman remained approximately the same. These differences between the effects of DFP and soman cannot be explained: 1) by differences in inhibition or de novo synthesis of AChE in various regions of the CNS, the striated muscle or blood, 2) by differences in the reductions of the muscarinic receptors in various regions of the CNS, 3) by differences in the number of nicotinic receptors in the diaphragm muscle, or 4) by differences in phosphorylphosphatase (DFP-ase or somanase) activity in blood plasma or liver.
van Dongen
C J
CJ
Medical Biological Laboratory TNO, Rijswijk, The Netherlands.
Wolthuis
O L
OL
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004361:Drug Tolerance; D007279:Injections, Subcutaneous; D007531:Isoflurophate / Q000494:pharmacology*; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism
D009943:Organophosphorus Compounds; D011976:Receptors, Muscarinic; D007531:Isoflurophate; D000110:Acetylcholinesterase