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Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus.
Br J Pharmacol 2013; 170(3):641-8BJ

Abstract

BACKGROUND AND PURPOSE

We evaluated the anti-emetic and anti-nausea properties of the acid precursor of Δ(9) -tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and determined its mechanism of action in these animal models.

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.

Authors+Show Affiliations

Department of Psychology, University of Guelph, Guelph, ON, Canada.No 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

23889598

Citation

Rock, E M., et al. "Tetrahydrocannabinolic Acid Reduces Nausea-induced Conditioned Gaping in Rats and Vomiting in Suncus Murinus." British Journal of Pharmacology, vol. 170, no. 3, 2013, pp. 641-8.
Rock EM, Kopstick RL, Limebeer CL, et al. Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus. Br J Pharmacol. 2013;170(3):641-8.
Rock, E. M., Kopstick, R. L., Limebeer, C. L., & Parker, L. A. (2013). Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus. British Journal of Pharmacology, 170(3), pp. 641-8. doi:10.1111/bph.12316.
Rock EM, et al. Tetrahydrocannabinolic Acid Reduces Nausea-induced Conditioned Gaping in Rats and Vomiting in Suncus Murinus. Br J Pharmacol. 2013;170(3):641-8. PubMed PMID: 23889598.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus. AU - Rock,E M, AU - Kopstick,R L, AU - Limebeer,C L, AU - Parker,L A, PY - 2013/02/27/received PY - 2013/07/05/revised PY - 2013/07/19/accepted PY - 2013/7/30/entrez PY - 2013/7/31/pubmed PY - 2014/8/20/medline KW - CB1 receptor KW - SR141716 KW - THC KW - THCA KW - conditioned gaping KW - vomiting SP - 641 EP - 8 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 170 IS - 3 N2 - BACKGROUND AND PURPOSE: We evaluated the anti-emetic and anti-nausea properties of the acid precursor of Δ(9) -tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and determined its mechanism of action in these animal models. 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/23889598/Tetrahydrocannabinolic_acid_reduces_nausea_induced_conditioned_gaping_in_rats_and_vomiting_in_Suncus_murinus_ L2 - https://doi.org/10.1111/bph.12316 DB - PRIME DP - Unbound Medicine ER -