Pharmacological analysis of diisopropyl fluorophosphate: effects on core temperature, heart rate, and motor activity in the unrestrained rat.
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 prostaglandin synthesis, administered during the period of DFP-induced hyperthermia produced a transient recovery in body temperature. Overall, DFP-induced hypothermia and hyperthermia in the rat appear to be mediated via cholinergic activation in the CNS because both are blocked by scopolamine. The decrease in core temperature following sodium salicylate suggests that prostaglandin release is involved in the manifestation of DFP-induced hyperthermia. The elevation in core temperature after DFP appears to involve neurochemical pathways similar to that of fever.
Gordon
C J
CJ
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000768:Anesthesia, General; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D007531:Isoflurophate / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid; D012601:Scopolamine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D012459:Salicylates; D007531:Isoflurophate; D011433:Propranolol; D012601:Scopolamine; D020156:Salicylic Acid