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Cannabidiolic acid enhances 5-HT1A receptor activation and prevents vomiting in Suncus murinus and nausea-like behaviour in rats with greater potency and selectivity than cannabidiol

Bolognini, D., Rock, E.M., Cluny, N.L., Cascio, M.G., Limebeer, C.L., Duncan, M., Stott, C.G., Javid, Farideh A., Parker , L.A. and Pertwee , R.G. (2013) Cannabidiolic acid enhances 5-HT1A receptor activation and prevents vomiting in Suncus murinus and nausea-like behaviour in rats with greater potency and selectivity than cannabidiol. British Journal of Pharmacology, 168 (6). pp. 1456-1470. ISSN 0007-1188

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Abstract

Background and Purpose

To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT1A receptor activation in animal models.
Experimental Approach

We investigated the effect of CBDA on (i) lithium chloride (LiCl)-induced conditioned gaping to a flavour (nausea-induced behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin palatability in rats; (iii) motion-, LiCl- or cisplatin-induced vomiting in house musk shrews (Suncus murinus); and (iv) rat brainstem 5-HT1A receptor activation by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and mouse whole brain CB1 receptor activation by CP55940, using [35S]GTPγS-binding assays.
Key Results

In shrews, CBDA (0.1 and/or 0.5 mg·kg−1 i.p.) reduced toxin- and motion-induced vomiting, and increased the onset latency of the first motion-induced emetic episode. In rats, CBDA (0.01 and 0.1 mg·kg−1 i.p.) suppressed LiCl- and context-induced conditioned gaping, effects that were blocked by the 5-HT1A receptor antagonist, WAY100635 (0.1 mg·kg−1 i.p.), and, at 0.01 mg·kg−1 i.p., enhanced saccharin palatability. CBDA-induced suppression of LiCl-induced conditioned gaping was unaffected by the CB1 receptor antagonist, SR141716A (1 mg·kg−1 i.p.). In vitro, CBDA (0.1–100 nM) increased the Emax of 8-OH-DPAT.
Conclusions and Implications

Compared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5-HT1A receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Schools: School of Applied Sciences
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Depositing User: Graham Stone
Date Deposited: 30 Oct 2012 12:08
Last Modified: 05 Jun 2013 13:01
URI: http://eprints.hud.ac.uk/id/eprint/15806

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