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.

Hypothermia and delayed fever in the male and female rat exposed to chlorpyrifos.

Chlorpyrifos (CHL) is a commonly used organophosphate (OP) pesticide which irreversibly inhibits acetylcholinesterase activity in the CNS. Little is known regarding the thermoregulatory effects of CHL when administered orally and whether the sensitivity to CHL is affected by sex. To address these issues, male and female rats of the Long-Evans strain were administered 0, 10, 50, or 80 mg/kg CHL by gavage while core temperature (T(c)) and motor activity (MA) were monitored continuously by telemetry. Females were generally more sensitive than males to CHL. Significant hypothermic responses to CHL were observed in males administered 80 mg/kg and in females administered 10-80 mg/kg. Following recovery from hypothermia T(c) of both males and females underwent a significant elevation during the light phase 1-2 days after CHL exposure. CHL-induced hyperthermia was blocked in male and female rats by administration of 200 mg/kg sodium salicylate (SS), an antipyretic agent. Male castrated rats were markedly more sensitive to the hypothermic and hyperthermic effects of CHL compared to sham operated controls. On the other hand, ovariectomized female rats responded to CHL in a similar fashion as the sham operated controls. Thus, testicular function may be important in determining greater resistance to CHL in male rats. It appears that exposure to CHL leads to a delayed fever which involves activation of CNS pathways normally involved in fever. This mechanism could be responsible for the febrile response to OP pesticides commonly observed in humans exposed to OPs.