期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 168, 期 6, 页码 1456-1470出版社
WILEY
DOI: 10.1111/bph.12043
关键词
cannabidiolic acid; 5-HT1A receptor; rat; shrew; conditioned gaping; anticipatory nausea; taste reactivity; toxin-induced vomiting; motion-induced vomiting; emesis
资金
- GW Pharmaceuticals
- National Institute on Drug Abuse [DA-03672]
- Natural Sciences and Engineering Council of Canada [NSERC-92057]
- GW Research Ltd, UK
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]GTPS-binding assays. Key Results In shrews, CBDA (0.1 and/or 0.5mg center dot kg1 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 0.1mg center dot kg1 i.p.) suppressed LiCl- and context-induced conditioned gaping, effects that were blocked by the 5-HT1A receptor antagonist, WAY100635 (0.1mg center dot kg1 i.p.), and, at 0.01mg center dot kg1 i.p., enhanced saccharin palatability. CBDA-induced suppression of LiCl-induced conditioned gaping was unaffected by the CB1 receptor antagonist, SR141716A (1mg center dot kg1 i.p.). In vitro, CBDA (0.1100nM) 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.
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