Thermoregulatory effects of resiniferatoxin in the rat

When administered acutely, the vanilloid (capsaicin) receptor agonist resiniferatoxin induces marked hypothermia in the ferret, rat and mouse. The aim of this study was to further characterise the thermoregulatory effects of resiniferatoxin in the rat in an attempt to understand the mechanism by which resiniferatoxin induces this hypothermic effect. Three doses of resiniferatoxin were administered (50, 100, 200 micrograms/kg s.c.) in separate animals at an ambient temperature (Ta) of 20 degrees C but there was no apparent dose-related effect on the decrease in colonic temperature over this range. Resiniferatoxin (50 micrograms/kg s.c.) decreased whole body oxygen consumption when measured below thermoneutrality (Ta = 20 degrees C) but not at thermoneutrality (Ta = 29 degrees C); likewise there was no hypothermic response to resiniferatoxin when measured at a Ta of 29 degrees C. Operant responding for radiant heat in a cold environment (-8 degrees C) was also measured in resiniferatoxin-treated (50 micrograms/kg s.c.) rats. These experiments showed that resiniferatoxin-treated rats attempted to defend body temperature by lever pressing for more radiant heat. However, this was not sufficient to reverse the hypothermia. Two repeat doses, 1 week apart, had little or no effect on colonic temperature, oxygen consumption or operant responding in the cold. Resiniferatoxin (50 micrograms/kg s.c.) also produced hypothermia (Ta = 20 degrees C) in neonatally capsaicinized adult rats. The exact site and mode of action is still under investigation, but it is postulated that resiniferatoxin activates, and then destroys or desensitizes warm thermoreceptors.