Effect of central and peripheral cholinergic antagonists on chlorpyrifos-induced changes in body temperature in the rat.
Exposure to the organophosphate (OP)-based pesticide chlorpyrifos (CHP) in the rat results in an initial period of hypothermia lasting < 24 h, followed by a fever lasting 48-72 h. The purpose of this study was to determine how cholinergic pathways participate in the mediation of the thermoregulatory effects of CHP. The corn oil (CO) vehicle or CHP (25 mg/kg; p.o.) was administered to female rats while core temperature (Tc) and motor activity (MA) were monitored by radiotelemetry. The peripheral muscarinic antagonist, methyl scopolamine (MS) and central antagonist, scopolamine (S) were administered during the period of CHP-induced hypothermia and fever. The hypothermia was attenuated by scopolamine but not by methyl scopolamine. The delayed fever was augmented by scopolamine but blocked by methyl scopolamine. The results indicate that CHP-induced hypothermia is mediated by cholinergic stimulation of heat loss pathways in CNS thermoregulatory centers. Peripheral cholinergic pathways appear to have a minimal role in mediating chlorpyrifos-induced hypothermia. On the other hand, the chlorpyrifos-induced fever appears to be mediated by a peripheral pathway that is blocked by methyl scopolamine. The data provides a possible explanation for the persistent fever in humans exposed to OP pesticides and treated with atropine. Methyl atropine or methyl scopolamine may be a more effective therapy in the treatment of the fever.
Gordon
C J
CJ
Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. gordon.christopher@epamail.epa.gov
Grantham
T A
TA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004390:Chlorpyrifos / Q000633:toxicity*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology; D007035:Hypothermia / Q000139:chemically induced / Q000503:physiopathology; D007306:Insecticides / Q000633:toxicity; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D019832:N-Methylscopolamine / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012601:Scopolamine / Q000494:pharmacology*
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D018727:Muscarinic Antagonists; D012601:Scopolamine; D004390:Chlorpyrifos; D019832:N-Methylscopolamine