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Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus.
Br J Pharmacol. 2012 Apr; 165(8):2620-34.BJ

Abstract

BACKGROUND AND PURPOSE

To evaluate the hypothesis that activation of somatodendritic 5-HT(1A) autoreceptors in the dorsal raphe nucleus (DRN) produces the anti-emetic/anti-nausea effects of cannabidiol (CBD), a primary non-psychoactive cannabinoid found in cannabis.

EXPERIMENTAL APPROACH

The potential of systemic and intra-DRN administration of 5-HT(1A) receptor antagonists, WAY100135 or WAY100635, to prevent the anti-emetic effect of CBD in shrews (Suncus murinus) and the anti-nausea-like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra-DRN administration of CBD to produce anti-nausea-like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5-HT(1A) receptors and to modify the ability of the 5-HT(1A) agonist, 8-OH-DPAT, to stimulate [(35) S]GTPγS binding in rat brainstem membranes.

KEY RESULTS

CBD suppressed nicotine-, lithium chloride (LiCl)- and cisplatin (20 mg·kg(-1) , but not 40 mg·kg(-1))-induced vomiting in the S. murinus and LiCl-induced conditioned gaping in rats. Anti-emetic and anti-nausea-like effects of CBD were suppressed by WAY100135 and the latter by WAY100635. When administered to the DRN: (i) WAY100635 reversed anti-nausea-like effects of systemic CBD, and (ii) CBD suppressed nausea-like effects, an effect that was reversed by systemic WAY100635. CBD also displayed significant potency (in a bell-shaped dose-response curve) at enhancing the ability of 8-OH-DPAT to stimulate [(35) S]GTPγS binding to rat brainstem membranes in vitro. Systemically administered CBD and 8-OH-DPAT synergistically suppressed LiCl-induced conditioned gaping.

CONCLUSIONS AND IMPLICATIONS

These results suggest that CBD produced its anti-emetic/anti-nausea effects by indirect activation of the somatodendritic 5-HT(1A) autoreceptors in the DRN.

LINKED ARTICLES

This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.

Authors+Show Affiliations

Department of Psychology and Neuroscience Graduate Program, University of Guelph, Guelph, ON, Canada.No 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

21827451

Citation

Rock, E M., et al. "Cannabidiol, a Non-psychotropic Component of Cannabis, Attenuates Vomiting and Nausea-like Behaviour Via Indirect Agonism of 5-HT(1A) Somatodendritic Autoreceptors in the Dorsal Raphe Nucleus." British Journal of Pharmacology, vol. 165, no. 8, 2012, pp. 2620-34.
Rock EM, Bolognini D, Limebeer CL, et al. Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. Br J Pharmacol. 2012;165(8):2620-34.
Rock, E. M., Bolognini, D., Limebeer, C. L., Cascio, M. G., Anavi-Goffer, S., Fletcher, P. J., Mechoulam, R., Pertwee, R. G., & Parker, L. A. (2012). Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. British Journal of Pharmacology, 165(8), 2620-34. https://doi.org/10.1111/j.1476-5381.2011.01621.x
Rock EM, et al. Cannabidiol, a Non-psychotropic Component of Cannabis, Attenuates Vomiting and Nausea-like Behaviour Via Indirect Agonism of 5-HT(1A) Somatodendritic Autoreceptors in the Dorsal Raphe Nucleus. Br J Pharmacol. 2012;165(8):2620-34. PubMed PMID: 21827451.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus. AU - Rock,E M, AU - Bolognini,D, AU - Limebeer,C L, AU - Cascio,M G, AU - Anavi-Goffer,S, AU - Fletcher,P J, AU - Mechoulam,R, AU - Pertwee,R G, AU - Parker,L A, PY - 2011/8/11/entrez PY - 2011/8/11/pubmed PY - 2012/7/28/medline SP - 2620 EP - 34 JF - British journal of pharmacology JO - Br J Pharmacol VL - 165 IS - 8 N2 - BACKGROUND AND PURPOSE: To evaluate the hypothesis that activation of somatodendritic 5-HT(1A) autoreceptors in the dorsal raphe nucleus (DRN) produces the anti-emetic/anti-nausea effects of cannabidiol (CBD), a primary non-psychoactive cannabinoid found in cannabis. EXPERIMENTAL APPROACH: The potential of systemic and intra-DRN administration of 5-HT(1A) receptor antagonists, WAY100135 or WAY100635, to prevent the anti-emetic effect of CBD in shrews (Suncus murinus) and the anti-nausea-like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra-DRN administration of CBD to produce anti-nausea-like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5-HT(1A) receptors and to modify the ability of the 5-HT(1A) agonist, 8-OH-DPAT, to stimulate [(35) S]GTPγS binding in rat brainstem membranes. KEY RESULTS: CBD suppressed nicotine-, lithium chloride (LiCl)- and cisplatin (20 mg·kg(-1) , but not 40 mg·kg(-1))-induced vomiting in the S. murinus and LiCl-induced conditioned gaping in rats. Anti-emetic and anti-nausea-like effects of CBD were suppressed by WAY100135 and the latter by WAY100635. When administered to the DRN: (i) WAY100635 reversed anti-nausea-like effects of systemic CBD, and (ii) CBD suppressed nausea-like effects, an effect that was reversed by systemic WAY100635. CBD also displayed significant potency (in a bell-shaped dose-response curve) at enhancing the ability of 8-OH-DPAT to stimulate [(35) S]GTPγS binding to rat brainstem membranes in vitro. Systemically administered CBD and 8-OH-DPAT synergistically suppressed LiCl-induced conditioned gaping. CONCLUSIONS AND IMPLICATIONS: These results suggest that CBD produced its anti-emetic/anti-nausea effects by indirect activation of the somatodendritic 5-HT(1A) autoreceptors in the DRN. LINKED ARTICLES: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/21827451/abstract/Cannabidiol_a_Non_Psychotropic_Component_of_Cannabis_Attenuates_Vomiting_and_Nausea_like_Behaviour_via_Indirect_Agonism_of_5_HT_1A__Somatodendritic:_Autoreceptors_in_the_Dorsal_Raphe_Nucleus_ L2 - https://doi.org/10.1111/j.1476-5381.2011.01621.x DB - PRIME DP - Unbound Medicine ER -