Strain differences in the laboratory rat: impact on the autonomic, behavioral, and biochemical response to cholinesterase inhibition.
Intraspecies variation has been found to affect the physiological, behavioral, and biochemical responses to a variety of neurotoxicants, including the organophosphate diisopropyl fluorophosphate (DFP). However, there is little information on long-term physiological responses to neurotoxicant exposure using strain as a dependent variable. In the present study, radiotelemetry methodology was used to continuously monitor core temperature, heart rate, and motor activity for 4 d following administration of 1.5 mg/kg DFP (sc) in four common strains of rat: Sprague-Dawley (SD), Long-Evans (LE), Fischer 344 (F344), and Wistar (WST). The F344 rat was least susceptible to DFP in terms of both a minimal hypothermic response and recovery of the day-night difference in core temperature. The SD strain was unusual in that its heart rate was elevated relative to the other strains after DFP, in spite of a marked decrease in core temperature and motor activity. The LE strain exhibited the largest reduction in core temperature and heart rate following DFP. Serum and brain cholinesterase activity (ChE) measured 3 h after administration of 1.0 mg/kg DFP also indicated strain effects. The F344 showed less inhibition in these variables compared to the other strains, a response that may explain its attenuated thermoregulatory response to DFP. Overall, the inbred F344 rat demonstrated better resistance to DFP compared to the outbred strains. Therefore, the impact of genetic differences on sensitivity to neurotoxicants such as DFP could be an important tool in understanding the mechanism of action of these agents.
Gordon
C J
CJ
Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
Watkinson
W P
WP
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism*; D014644:Genetic Variation; D006339:Heart Rate / Q000187:drug effects; D007279:Injections, Subcutaneous; D007531:Isoflurophate / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats / Q000235:genetics* / Q000502:physiology; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity
D007531:Isoflurophate; D002802:Cholinesterases