Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT(1A) receptor activation

D Bolognini, EM Rock, NL Cluny, MG Cascio, CL Limebeer, M Duncan, CG Stott, FA Javid, LA Parker, RG 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-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 [(35) S]GTP¿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, 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 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.
Original languageEnglish
Pages (from-to)1456-1470
Number of pages15
JournalBritish Journal of Pharmacology
Volume168
Issue number6
Early online date25 Feb 2013
DOIs
Publication statusPublished - Mar 2013

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

Keywords

  • cannabidiolic acid
  • 5-HT1A receptor
  • rat
  • shrew
  • conditioned gaping
  • anticipatory nausea
  • taste reactivity
  • toxin-induced vomiting
  • motion-induced vomiting
  • emesis

Cite this

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT(1A) receptor activation. / Bolognini, D; Rock, EM; Cluny, NL; Cascio, MG; Limebeer, CL; Duncan, M; Stott, CG; Javid, FA; Parker, LA; Pertwee, RG.

In: British Journal of Pharmacology, Vol. 168, No. 6, 03.2013, p. 1456-1470.

Research output: Contribution to journalArticle

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-HT(1A) receptor activation', British Journal of Pharmacology, vol. 168, no. 6, pp. 1456-1470. https://doi.org/10.1111/bph.12043
Bolognini, D ; Rock, EM ; Cluny, NL ; Cascio, MG ; Limebeer, CL ; Duncan, M ; Stott, CG ; Javid, FA ; Parker, LA ; Pertwee, RG. / Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT(1A) 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-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 [(35) S]GTP¿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, 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 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.",
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T1 - Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT(1A) receptor activation

AU - Bolognini, D

AU - Rock, EM

AU - Cluny, NL

AU - Cascio, MG

AU - Limebeer, CL

AU - Duncan, M

AU - Stott, CG

AU - Javid, FA

AU - Parker, LA

AU - Pertwee, RG

N1 - © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

PY - 2013/3

Y1 - 2013/3

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 [(35) S]GTP¿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, 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 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.

AB - 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 [(35) S]GTP¿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, 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 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.

KW - cannabidiolic acid

KW - 5-HT1A receptor

KW - rat

KW - shrew

KW - conditioned gaping

KW - anticipatory nausea

KW - taste reactivity

KW - toxin-induced vomiting

KW - motion-induced vomiting

KW - emesis

U2 - 10.1111/bph.12043

DO - 10.1111/bph.12043

M3 - Article

VL - 168

SP - 1456

EP - 1470

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 6

ER -