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On the development of behavioral tolerance to organophosphates. IV: EEGand visual evoked responses
O L Wolthuis1, I H Philippens, R A Vanwersch
1Medical Biological Laboratory TNO, Rijswijk, The Netherlands.
Abstract:
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 micrograms/kg) or soman (60 micrograms/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 (VERs) 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
This study investigated why repeated soman injections don't cause behavioral tolerance in rats, unlike DFP. Neurophysiological recordings of EEG and VERs revealed similar patterns across experiments, suggesting underlying similarities in organophosphate cholinesterase inhibitor effects.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Organophosphate cholinesterase inhibitors like soman and DFP have different effects on behavioral tolerance in rats.
- Previous research indicates that repeated soman injections do not induce behavioral tolerance, contrasting with DFP.
- The neurophysiological basis for this difference remains unclear.
Purpose of the Study:
- To investigate the neurophysiological differences between soman and DFP regarding behavioral tolerance.
- To compare electroencephalogram (EEG) and visual evoked responses (VERs) following acute and repeated exposure to soman and DFP.
- To elucidate the mechanisms underlying the differential development of tolerance to these two organophosphate cholinesterase inhibitors.
Main Methods:
- Four experiments (A, B, C, D) involving rats injected with saline, DFP, or soman.
- Behavioral training in a two-way shuttlebox for experiments B and D.
- Recording of EEG and VERs in freely moving rats after single and repeated injections of the compounds.
- Comparison of neurophysiological responses between trained and untrained animals.
Main Results:
- EEG and VERs showed similar patterns across all four experiments and treatment groups.
- DFP-treated rats developed behavioral tolerance after repeated injections.
- The neurophysiological recordings did not reveal significant differences that explained the behavioral tolerance disparity between soman and DFP.
Conclusions:
- Despite behavioral differences, the neurophysiological responses (EEG and VERs) to soman and DFP exhibit a similar pattern.
- The underlying mechanisms for the lack of behavioral tolerance to soman, compared to DFP, require further investigation beyond EEG and VER analysis.
- This study highlights the complexity of organophosphate toxicity and tolerance development.