Effects of d-amphetamine on behavioral and autonomic thermoregulation in mice

d-Amphetamine has well-known behavioral and sympathomimetic effects in rodents, but its effects on thermoregulation are not well characterized. d-Amphetamine was administered IP to mice at doses of 0.1 to 10.0 mg/kg. Locomotor activity and preferred ambient temperature (Ta) were measured for 60 min after injection in a linear temperature gradient, and metabolic rate (MR) and evaporative water loss (EWL) were measured in a metabolic chamber at ambient temperatures of either 20 degrees C or 30 degrees C. Colonic temperatures (Tc) were obtained 60 min after injection in all cases. Doses of d-amphetamine at 0.3 mg/kg and above reduced preferred Ta from the control value of 30 degrees C to about 25 degrees C. Locomotor activity was reduced briefly by 0.3 mg/kg, and increased after 3.0 mg/kg d-amphetamine. Metabolic rate was suppressed by 0.3 mg/kg of the drug at both 20 and 30 degrees C. At 20 degrees C Ta, 10.0 mg/kg d-amphetamine increased MR but not EWL. At 30 degrees C, MR and EWL were both increased by doses of 3.0 and 10.0 mg/kg. Body temperatures varied both as a function of d-amphetamine dose and of apparatus, with pronounced hyperthermia (Tc greater than 38.5 degrees C) evident only after 10 mg/kg in the metabolic chamber. Thus, the behavioral and autonomic heat loss responses induced in mice by d-amphetamine suggest that its thermogenic action is detected by the animal at doses below those producing measurable thermogenesis and that appropriate effectors, from selection of a cool Ta to increasing EWL, are engaged in an orderly progression to maintain normothermia under all but the most challenging conditions.