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Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation.
Br J Pharmacol 2013; 168(6):1456-70BJ

Abstract

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 (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 CB(1) 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-HT(1A) 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 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.

Authors+Show Affiliations

Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23121618

Citation

Bolognini, D, et al. "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, 2013, pp. 1456-70.
Bolognini D, Rock EM, Cluny NL, et al. Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation. Br J Pharmacol. 2013;168(6):1456-70.
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), pp. 1456-70. doi:10.1111/bph.12043.
Bolognini D, et al. Cannabidiolic Acid Prevents Vomiting in Suncus Murinus and Nausea-induced Behaviour in Rats By Enhancing 5-HT1A Receptor Activation. Br J Pharmacol. 2013;168(6):1456-70. PubMed PMID: 23121618.
* Article titles in AMA citation format should be in sentence-case
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,R G, PY - 2012/07/16/received PY - 2012/09/17/revised PY - 2012/10/12/accepted PY - 2012/11/6/entrez PY - 2012/11/6/pubmed PY - 2013/8/24/medline SP - 1456 EP - 70 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 168 IS - 6 N2 - 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 (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 CB(1) 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-HT(1A) 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 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/23121618/Cannabidiolic_acid_prevents_vomiting_in_Suncus_murinus_and_nausea_induced_behaviour_in_rats_by_enhancing_5_HT1A_receptor_activation_ L2 - https://doi.org/10.1111/bph.12043 DB - PRIME DP - Unbound Medicine ER -