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, beh avioral, and biochemical responses to a variety of neurotoxicants, inc luding the organophosphate diisopropyl fluorophosphate (DFP). However, there is little information on long-term physiological responses to n eurotoxicant exposure using strain as a dependent variable. In the pre sent study, radiotelemetry methodology was used to continuously monito r core temperature, heart rate, and motor activity for 4 d following a dministration of 1.5 mg/kg DFP (sc) in four common strains of rat: Spr ague-Dawley (SD), Long-Evans (LE), Fischer 344 (F344), and Wistar (WST ). The F344 rat was least susceptible to DFP in terms of both a minima l hypothermic response and recovery of the day-night difference in cor e temperature. The SD strain was unusual in that its heart rate was el evated relative to the other strains after DFP, in spite of a marked d ecrease in core temperature and motor activity. The LE strain exhibite d the largest reduction in core temperature and heart rate following D FP. Serum and brain cholinesterase activity (ChE) measured 3 h after a dministration of 1.0 mg/kg DFP also indicated strain effects. The F344 showed less inhibition in these variables compared to the other strai ns, a response that may explain its attenuated thermoregulatory respon se to DFP. Overall, the inbred F344 rat demonstrated better resistance to DFP compared to the outbred strains. Therefore, the impact of gene tic differences on sensitivity to neurotoxicants such as DFP could be an important tool in understanding the mechanism of action of these ag ents.