ACUTE EFFECTS OF DIISOPROPYL FLUOROPHOSPHATE (DFP) ON AUTONOMIC AND BEHAVIORAL THERMOREGULATORY RESPONSES IN THE LONG-EVANS RAT

Experiments were designed to assess the mechanisms of diisopropyl fluorophosphate (DFP)-induced changes in thermoregulation of the rat. In one study, male rats of the Long-Evans strain were injected with DFP (s.c.) at doses ranging from 0 to 2.0 mg/kg while maintained at an ambient temperature (T(a)) of 20-24-degrees-C. Body (T(b)) and tail skin (T(t)) temperatures were recorded for 5 h post-injection. DFP doses of greater-than-or-equal-to 1.0 mg/kg resulted in significant decreases in T(b) lasting up to 5 h and increases in T(t) lasting up to 1 h post-injection. In a second study, metabolic rate (MR), evaporative water loss (EWL), motor activity (MA), T(b), and T(t) were measured at 2 h post-injection of 0, 0.5, 1.0, and 1.5 mg/kg DFP (s.c.) at T(a) values of 10, 20, and 30-degrees-C. DFP treatment resulted in hypothermia at all three T(a) values, but the effect was attenuated at 30-degrees-C. MR was significantly reduced at a T(a) of 20-degrees-C following 1.5 mg/kg, unaffected by DFP at a T(a) of 30-degrees-C, and stimulated at 10-degrees-C following 0.5 mg/kg DFP. EWL was significantly elevated at 30-degrees-C following 1.5 mg/kg DFP. MA was significantly reduced following greater-than-or-equal-to 1.0 mg/kg DFP at 20 and 30-degrees-C and 1.5 mg/kg at 10-degrees-C. T(t) was elevated and reduced by DFP at T(a) values of 30 and 10-degrees-C, respectively. In a third study, rats were injected with DFP and placed in a temperature gradient for 1 to 2 h post-injection while selected T(a) and T(b) were monitored. While both control and DFP-treated rats remained in the cool end of the gradient, rats administered DFP at doses of 1.0 and 1.5 mg/kg were significantly hypothermic. It was also found that T(a) values of 10, 20, and 30-degrees-C had no effect on DFP-induced inhibition of cholinesterase activity of plasma and erythrocyte fractions of whole blood. Overall, these data support the hypothesis that acute DFP may lower the set-point for the control of body temperature in the rat and demonstrates that the toxicity of DFP is modified by changes in T(a).