Abstract | BACKGROUND AND PURPOSE: EXPERIMENTAL APPROACH: We investigated the effect of THCA on lithium chloride- (LiCl) induced conditioned gaping ( nausea-induced behaviour) to a flavour, and context (a model of anticipatory nausea) in rats, and on LiCl-induced vomiting in Suncus murinus. Furthermore, we investigated THCA's ability to induce hypothermia and suppress locomotion [rodent tasks to assess cannabinoid1 ( CB1 ) receptor agonist-like activity], and measured plasma and brain THCA and THC levels. We also determined whether THCA's effect could be blocked by pretreatment with SR141716 (SR, a CB1 receptor antagonist). KEY RESULTS: In rats, THCA (0.05 and/or 0.5 mg·kg(-1) ) suppressed LiCl-induced conditioned gaping to a flavour and context; the latter effect blocked by the CB1 receptor antagonist, SR, but not by the 5-hydroxytryptamine-1A receptor antagonist, WAY100635. In S. murinus, THCA (0.05 and 0.5 mg·kg(-1) ) reduced LiCl-induced vomiting, an effect that was reversed with SR. A comparatively low dose of THC (0.05 mg·kg(-1) ) did not suppress conditioned gaping to a LiCl-paired flavour or context. THCA did not induce hypothermia or reduce locomotion, indicating non-CB1 agonist-like effects. THCA, but not THC was detected in plasma samples. CONCLUSIONS AND IMPLICATIONS: THCA potently reduced conditioned gaping in rats and vomiting in S. murinus, effects that were blocked by SR. These data suggest that THCA may be a more potent alternative to THC in the treatment of nausea and vomiting.
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Authors | E M Rock, R L Kopstick, C L Limebeer, L A Parker |
Journal | British journal of pharmacology
(Br J Pharmacol)
Vol. 170
Issue 3
Pg. 641-8
(Oct 2013)
ISSN: 1476-5381 [Electronic] England |
PMID | 23889598
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2013 The British Pharmacological Society. |
Chemical References |
- Antiemetics
- Cannabinoid Receptor Antagonists
- Cnr1 protein, rat
- Receptor, Cannabinoid, CB1
- Dronabinol
- delta(9)-tetrahydrocannabinolic acid
- Lithium Chloride
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Topics |
- Animals
- Antiemetics
(blood, pharmacology)
- Behavior, Animal
(drug effects)
- Body Temperature Regulation
(drug effects)
- Brain
(drug effects, metabolism)
- Cannabinoid Receptor Antagonists
(pharmacology)
- Disease Models, Animal
- Dronabinol
(analogs & derivatives, blood, pharmacology)
- Lithium Chloride
- Male
- Motor Activity
(drug effects)
- Nausea
(blood, chemically induced, prevention & control, psychology)
- Rats
- Rats, Sprague-Dawley
- Receptor, Cannabinoid, CB1
(drug effects, metabolism)
- Shrews
- Time Factors
- Vomiting
(blood, chemically induced, prevention & control, psychology)
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