Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea.
BACKGROUND
Marijuana has been reported to suppress nausea produced by chemotherapy treatment in human cancer patients. Although there is abundant evidence that cannabinoid agonists attenuate vomiting in emetic species, there has been little experimental evidence of their anti-nausea potential. Considerable evidence suggests that conditioned rejection reactions in rats reflect nausea. The present experiments evaluated the potential of low doses of the cannabinoid agonists, delta-9-tetrahydrocannabinol (THC; 0.5 mg/kg, i.p.), and HU-210 (0.001 mg/kg and 0.01 mg/kg, i.p.), and the CB(1) antagonist SR-141716A in modulating the establishment and the expression of lithium-induced conditioned rejection reactions in rats.


OBJECTIVE
To evaluate the effect of cannabinoids on conditioned rejection reactions, a rat model of nausea.


METHODS
In experiments 1 and 2, respectively, rats were injected with cannabinoid agonists, THC (0.5 mg/kg, i.p.) and HU-210 (0.001, 0.005 or 0.01 mg/kg), 30 min prior to exposure to 0.1% saccharin solution by intraoral infusion. Immediately following saccharin exposure, they were injected with 20 ml/kg 0.15 M lithium chloride or saline. On each of two test trials, the rats were injected with the cannabinoid or vehicle 30 min prior to exposure to saccharin. In experiment 3, rats were injected with the CB(1) antagonist, SR-141716A (2.5 mg/kg) or a combination of SR-141716A and HU-210 (0.01 mg/kg) 30 min prior to an infusion of saccharin followed by injection of lithium or saline. They were given a single drug-free test trial. Experiment 4 replicated and extended the findings of experiment 3.


RESULTS
delta-9-THC and HU-210 interfered with the establishment and the expression of lithium-induced conditioned rejection reactions. The suppressive effect of HU-210 on rejection reactions was reversed by pretreatment with SR-141716A. Administration of SR-141716A prior to conditioning potentiated lithium-induced conditioned rejection reactions.


CONCLUSIONS
These results indicate that the establishment and the expression of lithium-induced conditioned rejection reactions are suppressed by pretreatment with cannabinoid agents. These effects appear to be mediated by their action on the CB(1) receptor, because they are reversed by pretreatment with SR-141716A. Finally, our results suggest that endogenous cannabinoids play a role in modulation of nausea, because the antagonist potentiated lithium-induced nausea.
Parker
Linda A
LA
Department of Psychology, Wilfrid Laurier University, Waterloo, Ontario, Canada N2L 3C5. lparker@wlu.ca
Mechoulam
Raphael
R
Schlievert
Coralynn
C
Abbott
Laura
L
Fudge
Melissa L
ML
Burton
Page
P
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002186:Cannabinoids / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077285:Rimonabant
D000932:Antiemetics; D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D013759:Dronabinol; D008094:Lithium; C062018:HU 211; D000077285:Rimonabant