On the development of behavioral tolerance to organophosphates. III: Behavioral aspects.

As part of a study on the mechanisms underlying behavioral tolerance to cholinesterase-inhibiting organophosphates (OP's) the present investigation was focussed on behavioral procedures affecting the development of tolerance. The effects of chronic administration of the OP's DFP (600 micrograms/kg SC) and soman (60 micrograms/kg SC) were compared in rats. These doses do not cause detectable effects upon close observation of the animals. As was found before, behavioral tolerance developed following DFP, but not following soman. Repeated behavioral testing affected the development of tolerance. Cross-tolerance between these two inhibitors was not found. Surprisingly, when DFP was administered 48 hr after soman, all animals were observationally normal, and when soman was given 48 hr after DFP the majority of the animals died. This indicates that the sequence in which these inhibitors were administered was of major importance. It is concluded that practice-related and/or state-dependent factors are important for the development of behavioral tolerance and that one should be careful in making generalizing statements about tolerance to cholinesterase-inhibiting OP's.