Phentolamine and thermoregulation in rats

Phentolamine (PHEN), a nonselective alpha-adrenoceptor antagonist, causes a dose and ambient temperature (Ta)-dependent fall in body temperature (Tb) when injected intraperitoneally. In this paper, we investigated whether this was caused by integrated behavioral and autonomic thermoregulatory responses and whether it was due to a central action of the drug. Male rats were trained to press a bar for warm air in the cold or cold air in the heat. Rats were tested in both conditions near their Tb peaks and troughs after injections of saline or PHEN (5 and 10 mg/kg, IP). Tb fell significantly within the first 30 min post-PHEN, and after that, in the cold, the rats worked to increase Ta. In the heat they did not change Ta. To determine what was responsible for the Tb fall, we measured heat loss and heat production after saline or PHEN (10 mg/kg; IP) at Ta 2, 20, and 30 degrees C. Decreases in Tb at 2 and 20 degrees C were caused by increased heat loss during the first 15-30 min post-PHEN. At 2 degrees C, heat production increased after the drop in Tb. We conclude that the main reason the rats do not start to work immediately to prevent their core temperature from falling is that skin temperature is high, due to peripheral vasodilation, and that skin temperature is the major stimulus for regulating preferred Ta. We believe these effects are mediated by peripheral mechanisms because intracerebro-ventricular injections of PHEN did not cause a fall in Tb.