Pharmacological analysis of diisopropyl fluorophosphate: effects on core temperature, heart rate, and motor activity in the unrestrained rat
Abstract
Humans acutely exposed to anticholinesterase (anti-ChE) pesticides often become febrile, whereas rats and other rodents become markedly hypothermic. The rat may nonetheless be a useful model for anti-ChE toxicity because recent work using radiotelemetry demonstrated an elevation in core temperature of unrestrained rats for several days following acute exposure to the anti-ChE, diisopropyl fluorophosphate (DFP). To discern the mechanisms of DFP-induced hypothermia and hyperthermia, various pharmacological agents were administered acutely or chronically to rats injected with 1.5 mg/kg DFP (SC). Core temperature, heart rate, and motor activity were monitored continuously via radiotelemetry. Methylscopolamine, a peripheral muscarinic antagonist, attenuated the DFP-induced hypothermia by 1.0 degree C and reversed the DFP-induced bradycardia. Chronic scopolamine, a central and peripheral muscarinic antagonist, delivered via a subcutaneously implanted minipump (9.5 mg/kg/day) blocked DFP-induced hypothermia and hyperthermia. Propranolol (10 mg/kg; SC), a general beta blocker, augmented the bradycardic effects of DFP but had no effect on body temperature. Sodium salicylate (200 and 300 mg/kg; IP), an antipyretic that inhibits prostagla...Continue Reading
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