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On the development of behavioral tolerance to organophosphates IV: EEG and visual evoked responses

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Author: Wolthuis, O.L. · Philippens, I.H.C.H.M. · Vanwersch, R.A.P.
Institution: Medisch Biologisch Laboratorium TNO · MBL
Source:Pharmacology Biochemistry and Behavior, 4, 39, 851-858
Identifier: 231609
doi: doi:10.1016/0091-3057(91)90043-2
Keywords: Vision · DFP · EEG · Organophosphates · Soman · Tolerance · VER · Dyflos · Soman · Animal experiment · Behavior · Controlled study · Drug tolerance · Electric shock · Electroencephalogram · Evoked visual response · Male · Nonhuman · Pupil · RatS · Rectum temperature · Animal · Behavior, Animal · Body Temperature · Conditioning, Operant · Drug Tolerance · Electroencephalography · Electroshock · Evoked Potentials, Visual · Isoflurophate · Male · Organophosphorus Compounds · Rats, Inbred Strains · Isoflurophate, 55-91-4 · Organophosphorus Compounds · Soman, 96-64-0


Several earlier studies showed that, in contrast with DFP, repeated injections with soman did not lead to behavioral tolerance in rats. The reason for the difference between the effects of these two organophosphate cholinesterase inhibitors was not clear and a neurophysiological approach was undertaken. Four experiments (A, B, C and D) were carried out, each consisting of three groups of rats, SC injected with saline, DFP (600 μg/kg) or soman (60 μg/kg) respectively. In Experiment B and D the rats were trained to criterion in a two-way shuttlebox. Thereafter, the animals of Experiment B were fitted with suitable electrodes and two days later their EEGs and visual evoked responses (VFRs) were recorded, 1 and 24 h after a single dose of the above-mentioned compounds. In Experiment D the trained animals were subsequently injected 3 times per week for 4 weeks with the same doses and their performance was tested 5 days per week, 1 and 24 h after injection. After those 4 weeks, when the DFP-treated animals had developed behavioral tolerance, electrodes were fitted and EEGs and VERs were recorded after two days, again 1 and 24 h after injection, as in Experiment B. The difference with Experiments A and C was that these animals were not trained. Otherwise, treatment schedules and recording procedures of Experiment A were identical to those of Experiments B and of Experiment C to those of Experiment D. In all cases the EEGs and VERs were recorded from animals slowly walking in a rotating hollow transparent wheel. The results show a similar pattern in all four experiments. The shapes of the averaged VERs remained essentially the same in all experiments; differences in latencies and amplitudes, which were observed 1 h after the injections of the cholinesterase inhibitors and had disappeared 23 h later, were interpreted as being quantitative in nature. On the other hand, the EEGs showed qualitative differences between the effects of the two organophosphates in all experiments, notably a clearcut extra peak in the low frequency range (2-2.5 Hz) of the EEG power spectrum 1 h after injection of soman, which had disappeared 23 hours later. A slight increase in beta-activity following soman was noted, but was not consistently present in all experiments. The EEG power spectra 24 h after the injection of both organophosphates only showed a high degree of synchronization in the 8 Hz range, compared with their respective saline-injected controls. The differences found could not be ascribed to changes in body temperature, pupil diameter or sensitivity to footshock. It is suggested that this extra peak detectable 1 hour after soman is due to a second, reversible effect of this compound, unrelated to its cholinesterase-inhibiting effect. This low frequency peak may be linked to the persistently recurring behavioral decrements found 1 h after the soman injections and may camouflage the detection or prevent the development of behavioral tolerance to the cholinesterase-inhibiting effects of soman.