Characterization of the hypothermic effect of the synthetic cannabinoid HU-210 in the rat. Relation to the adrenergic system and endogenous pyrogens.
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.
Ovadia
H
H
Department of Neurology, Hadassah University Hospital, Jerusalem, Israel.
Wohlman
A
A
Mechoulam
R
R
Weidenfeld
J
J
D000818:Animals; D002186:Cannabinoids / Q000096:biosynthesis*; D003000:Clonidine / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007035:Hypothermia / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology; D008297:Male; D011749:Pyrogens / Q000378:metabolism*; D051381:Rats; D013696:Temperature; D013997:Time Factors
D002186:Cannabinoids; D007375:Interleukin-1; D011749:Pyrogens; D013759:Dronabinol; D015232:Dinoprostone; D003000:Clonidine; C062018:HU 211