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Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea.
Psychopharmacology (Berl) 2003; 166(2):156-62P

Abstract

RATIONALE

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.

OBJECTIVES

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.

Authors+Show Affiliations

Department of Psychology, Wilfrid Laurier University, Waterloo, Ontario, Canada N2L 3C5. lparker@wlu.caNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12528012

Citation

Parker, Linda A., et al. "Effects of Cannabinoids On Lithium-induced Conditioned Rejection Reactions in a Rat Model of Nausea." Psychopharmacology, vol. 166, no. 2, 2003, pp. 156-62.
Parker LA, Mechoulam R, Schlievert C, et al. Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea. Psychopharmacology (Berl). 2003;166(2):156-62.
Parker, L. A., Mechoulam, R., Schlievert, C., Abbott, L., Fudge, M. L., & Burton, P. (2003). Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea. Psychopharmacology, 166(2), pp. 156-62.
Parker LA, et al. Effects of Cannabinoids On Lithium-induced Conditioned Rejection Reactions in a Rat Model of Nausea. Psychopharmacology (Berl). 2003;166(2):156-62. PubMed PMID: 12528012.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea. AU - Parker,Linda A, AU - Mechoulam,Raphael, AU - Schlievert,Coralynn, AU - Abbott,Laura, AU - Fudge,Melissa L, AU - Burton,Page, Y1 - 2003/01/15/ PY - 2002/06/16/received PY - 2002/10/24/accepted PY - 2003/1/16/pubmed PY - 2003/4/4/medline PY - 2003/1/16/entrez SP - 156 EP - 62 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 166 IS - 2 N2 - RATIONALE: 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. OBJECTIVES: 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. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/12528012/Effects_of_cannabinoids_on_lithium_induced_conditioned_rejection_reactions_in_a_rat_model_of_nausea_ L2 - https://dx.doi.org/10.1007/s00213-002-1329-2 DB - PRIME DP - Unbound Medicine ER -