The purpose of the present study was to identify the effects of an acute injection of a dual dopamine (DA)/noradrenaline (NA) reuptake inhibitor (bupropion) on exercise performance, thermoregulation and neurotransmitters in the preoptic area and anterior hypothalamus (PO/AH) of the rat during exercise in the heat. Body core temperature (T(core)), brain temperature (T(brain)) and tail skin temperature (T(tail)) were measured. A microdialysis probe was inserted in the PO/AH, and samples for measurement of extracellular DA, NA and serotonin (5-HT) levels were collected. Rats received either bupropion (17 mg kg(-1); hot-BUP) or saline (1 ml kg(-1); hot) 20 min before the start of exercise and ran at a speed of 26 m min(-1) until exhaustion in a warm environment (30 degrees C). Rats also ran until exhaustion in a cool environment (18 degrees C; cool). Running time to exhaustion was significantly influenced by the ambient temperature, and it was increased by bupropion in the heat (cool, 143.6 +/- 21 min; hot, 65.8 +/- 13 min; hot-BUP, 86.3 +/- 7.2 min). T(core) and T(brain) at exhaustion were significantly higher in the bupropion group compared to the cool and hot groups, respectively. T(tail) measured at exhaustion was not significantly different between the two hot conditions. Extracellular concentrations of DA and NA in the PO/AH increased during exercise, and was significantly higher in the bupropion than in cool and hot groups (P < 0.05). No differences were observed between groups for 5-HT levels. These results suggest that DA and NA in the PO/AH might be responsible for the increase in exercise performance and T(core) and T(brain) in the bupropion group in hyperthermia. Moreover, these results support previous findings in humans that acute bupropion ingestion increases T(core) during exercise in the heat, indicating the possibility of an important role for DA and NA in thermoregulation.