In the present study we have characterized the hypothermic effect of the psychoactive
cannabinoid HU-210, by investigating its interaction with the endogenous
pyrogens,
IL-1 and
PGE2. We also studied the involvement of the
adrenergic system in mediation of this hypothermic effect. Injection of
HU-210 directly into the preoptic area caused a dose dependent reduction of rectal temperature from 37 to 32.1 degrees C. Injection of the non-psychoactive analog,
HU-211 which does not bind to brain
cannabinoid receptor, did not affect body temperature. Injection of the
adrenergic agonists,
CGP-12177 and
clonidine (beta, and
alpha adrenergic agonists, respectively) abrogated the
hypothermia induced by
HU-210. Injection of the
adrenergic antagonists,
prazosin (alpha 1) and
propranolol (beta) enhanced the hypothermic effect of
HU-210. Intracerebral administration of
IL-1 or
PGE2 to rats pretreated with
HU-210 caused a transient inhibition of the
hypothermia. The ex vivo rate of basal or bacterial
endotoxin-induced synthesis of
PGE2 by different brain regions, including the preoptic area was not affected by
HU-210 administration. These results suggest that the synthetic
cannabinoid HU-210 acts in the preoptic area, probably via the brain
cannabinoid receptor to induce
hypothermia. The hypothermic effect can be antagonized by
adrenergic agonists and enhanced by
adrenergic antagonists.
HU-210 does not interfere with the pyrogenic effect of
IL-1 or
PGE2.