Abstract

Strain differences in response of aggregated Swiss Webster and BDF₁ mice to d-amphetamine were investigated at three environmental temperatures of 19, 23 and 27°C. At 19°C the Swiss Webster strain of mice exhibited the aggregate toxicity to d-amphetamine whereas the BDF strain did not. An increase in ambient room temperature resulted in the appearance of amphetamine aggregate toxicity in the BDF₁ strain. The toxicity also increased in the Swiss Webster strain at the higher room temperatures. The strain difference in mortality at 19°C was unrelated to brain levels or metabolism of d-amphetamine. Although hyperthermia was noted at all temperatures studied, the BDF strain responded to a lesser degree than the Swiss Webster strain. An increase in room temperature resulted in an increase in amphetamine-induced hyperthermia. These results indicate that the magnitude of this pharmacogenetic difference is dependent on room temperature, that pharmacokinetic factors are not involved in the difference and that a thermoregulatory difference between the strains is a factor in the strain difference in toxicity.