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Cannabidiolic acid prevents vomiting in S uncus murinus and nausea‐induced behaviour in rats by enhancing 5‐ HT 1A receptor activation
Author(s) -
Bolognini D,
Rock EM,
Cluny NL,
Cascio MG,
Limebeer CL,
Duncan M,
Stott CG,
Javid FA,
Parker LA,
Pertwee RG
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12043
Subject(s) - pharmacology , context (archaeology) , chemistry , saccharin , antagonist , agonist , receptor antagonist , motion sickness , pertussis toxin , endocrinology , medicine , receptor , biology , g protein , biochemistry , paleontology , radiology
Background and Purpose To evaluate the ability of cannabidiolic acid ( CBDA ) to reduce nausea and vomiting and enhance 5‐ HT 1A 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 ( S uncus murinus ); and (iv) rat brainstem 5‐ HT 1A receptor activation by 8‐hydroxy‐2‐(di‐ n ‐propylamino)tetralin (8‐ OH‐DPAT ) and mouse whole brain CB 1 receptor activation by CP 55940, using [ 35 S ] GTP γ S ‐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‐ HT 1A receptor antagonist, WAY 100635 (0.1 mg·kg −1 i.p.), and, at 0.01 mg·kg −1 i.p., enhanced saccharin palatability. C BDA ‐induced suppression of LiCl ‐induced conditioned gaping was unaffected by the CB 1 receptor antagonist, SR141716A (1 mg·kg −1 i.p.). In vitro , CBDA (0.1–100 nM ) increased the E max 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‐ HT 1A 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.