Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation

D. Bolognini, E. M. Rock, N. L. Cluny, M. G. Cascio, C. L. Limebeer, M. Duncan, C. G. Stott, F. A. Javid, L. A. Parker, Roger G. Pertwee

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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-HT 1A 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.

LanguageEnglish
Pages1456-1470
Number of pages15
JournalBritish Journal of Pharmacology
Volume168
Issue number6
DOIs
Publication statusPublished - 1 Mar 2013

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Receptor, Serotonin, 5-HT1A
Nausea
Vomiting
Lithium Chloride
Shrews
8-Hydroxy-2-(di-n-propylamino)tetralin
Cannabinoid Receptor CB1
Saccharin
rimonabant
Aptitude
Anticipatory Vomiting
Cannabidiol
Serotonin 5-HT1 Receptor Antagonists
Emetics
cannabidiolic acid
Cisplatin
Brain Stem
Animal Models
Brain

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Bolognini, D., Rock, E. M., Cluny, N. L., Cascio, M. G., Limebeer, C. L., Duncan, M., ... Pertwee, R. G. (2013). Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. British Journal of Pharmacology, 168(6), 1456-1470. https://doi.org/10.1111/bph.12043
Bolognini, D. ; Rock, E. M. ; Cluny, N. L. ; Cascio, M. G. ; Limebeer, C. L. ; Duncan, M. ; Stott, C. G. ; Javid, F. A. ; Parker, L. A. ; Pertwee, Roger G. / Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. In: British Journal of Pharmacology. 2013 ; Vol. 168, No. 6. pp. 1456-1470.
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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-HT 1A 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.",
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Bolognini, D, Rock, EM, Cluny, NL, Cascio, MG, Limebeer, CL, Duncan, M, Stott, CG, Javid, FA, Parker, LA & Pertwee, RG 2013, 'Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation', British Journal of Pharmacology, vol. 168, no. 6, pp. 1456-1470. https://doi.org/10.1111/bph.12043

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. / Bolognini, D.; Rock, E. M.; Cluny, N. L.; Cascio, M. G.; Limebeer, C. L.; Duncan, M.; Stott, C. G.; Javid, F. A.; Parker, L. A.; Pertwee, Roger G.

In: British Journal of Pharmacology, Vol. 168, No. 6, 01.03.2013, p. 1456-1470.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation

AU - Bolognini, D.

AU - Rock, E. M.

AU - Cluny, N. L.

AU - Cascio, M. G.

AU - Limebeer, C. L.

AU - Duncan, M.

AU - Stott, C. G.

AU - Javid, F. A.

AU - Parker, L. A.

AU - Pertwee, Roger G.

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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-HT 1A 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.

AB - 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-HT 1A 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.

KW - 5-HT receptor

KW - anticipatory nausea

KW - cannabidiolic acid

KW - conditioned gaping

KW - emesis

KW - motion-induced vomiting

KW - rat

KW - shrew

KW - taste reactivity

KW - toxin-induced vomiting

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DO - 10.1111/bph.12043

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T2 - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

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ER -