Factors influencing diisopropyl fluorophosphate-induced hypothermia and hyperthermia in the rat.
Exposing rats to the anticholinesterase (anti-ChE) diisopropyl fluorophosphate (DFP) causes a transient period of hypothermia followed by a period of hyperthermia lasting approximately 48 h. Because a fever is a predominant thermoregulatory response in humans exposed to anti-ChE pesticides, the hyperthermic response in the rat may be important to understanding the central neural mechanisms of anti-ChEs. The purpose of the present study was to assess the dependence of DFP-induced thermoregulatory changes on basal behavioral and autonomic activity in the rat. Core temperature (Tc), heart rate (HR), and motor activity (MA) were monitored via radiotelemetry in unrestrained rats 24 h prior to and 72 h after administration of the peanut oil vehicle or 1.5 mg/kg DFP. Mean Tc decreased by approximately 4 degrees C by 4 h after DFP, returned to baseline by 27 h, and then remained approximately 0.8 degrees C above control daytime levels during the second day after DFP injection. Correlations of DFP-induced hypothermia and hyperthermia with baseline Tc, HR, and MA were performed. The baseline Tc was inversely correlated with the magnitude of DFP-induced hyperthermia (r2 = 0.6). DFP-induced hyperthermia was also inversely correlated with baseline HR and MA. The minimum core temperature during DFP-induced hypothermia was directly correlated with the baseline Tc. The inverse pattern between baseline Tc and DFP-induced hyperthermia is similar to that of rats administered endotoxin and other pyrogenic agents. Sixty percent of the variation in DFP-induced hyperthermia, a toxic response seen > 48 h after exposure, can be explained by individual differences in baseline Tc. This relationship may be important in understanding the thermoregulatory and metabolic effects of anti-ChE agents.
Gordon
C J
CJ
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003864:Depression, Chemical; D005334:Fever / Q000139:chemically induced*; D006339:Heart Rate / Q000187:drug effects; D007035:Hypothermia / Q000139:chemically induced*; D007531:Isoflurophate / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D013268:Stimulation, Chemical; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D007531:Isoflurophate