THERMOREGULATORY EFFECTS OF RESINIFERATOXIN IN THE RAT

When administered acutely, the vanilloid (capsaicin) receptor agonist resiniferatoxin induces marked hypothermia in the ferret, rat and mous e. The aim of this study was to further characterise the thermoregulat ory 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 mu g/ kg s.c.) in separate animals at an ambient temperature (T-a) of 20 deg rees C but there was no apparent dose-related effect on the decrease i n colonic temperature over this range. Resiniferatoxin (50 mu g/kg s.c .) decreased whole body oxygen consumption when measured below thermon eutrality (T-a = 20 degrees C) but not at thermoneutrality (T-a = 29 d egrees C); likewise there was no hypothermic response to resiniferatox in when measured at a T-a of 29 degrees C. Operant responding for radi ant heat in a cold environment (-8 degrees C) was also measured in res iniferatoxin-treated (50 mu g/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 suffic ient to reverse the hypothermia. Two repeat doses, 1 week apart, had l ittle or no effect on colonic temperature, oxygen consumption or opera nt responding in the cold. Resiniferatoxin (50 mu g/kg s.c.) also prod uced hypothermia (T-a = 20 degrees C) in neonatally capsaicinized adul t rats. The exact site and mode of action is still under investigation , but it is postulated that resiniferatoxin activates, and then destro ys or desensitizes warm thermoreceptors.