Cholinergic and opiate involvement in the antinociceptive effect of diisopropylfluorophosphate

The organophosphate diisopropylfluorophosphate (DFP; 3 or 6 mg/kg, IP) caused a dose-related antinociception in mice which was antagonized by the muscarinic antagonist scopolamine. The opiate antagonist naloxone antagonized the antinociceptive effect of the highest dose of DFP, but did not affect the antinociception caused by 3 mg/kg DFP. Twenty-four hours after the administration of DFP, reaction time in animals which received a 3 mg/kg dose did not differ from control. However, reaction time was still significantly higher than control in mice administered 6 mg/kg DFP twenty-four hours earlier. This residual antinociception was antagonized by naloxone but not by scopolamine, suggesting that it was opioid in nature. These results suggest that antinociception induced by a low dose of DFP is primarily due to a cholinergic mechanism, while higher doses appear to affect also the opiate system. Since we have previously shown that DFP (6 mg/kg) increases met-enkephalin levels in brain, it is possible that high doses of DFP might interfere with enkephalin metabolizing enzymes. This conclusion cannot be extended to the organophosphate disulfoton, whose antinociception, even at high doses, appears to involve only an interaction with the cholinergic system.