大麻的非精神活性成分大麻二酚通过在中缝背核中间接激动 5-HT(1A) 体树突自受体，减弱呕吐和类似恶心的行为。
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.
机构信息
Department of Psychology and Neuroscience Graduate Program, University of Guelph, Guelph, ON, Canada.
出版信息
Br J Pharmacol. 2012 Apr;165(8):2620-34. doi: 10.1111/j.1476-5381.2011.01621.x.
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.
背景和目的
评估这样一种假设，即中脑导水管周围灰质（DRN）中的 5-羟色胺（5-HT）1A 自受体的激活产生大麻素（CBD）的止吐/止恶心作用，CBD 是大麻中发现的主要非精神活性大麻素。
实验方法
评估全身性和 DRN 内给予 5-HT1A 受体拮抗剂 WAY100135 或 WAY100635 以预防 CBD 在鼩鼱（Suncus murinus）中的止吐作用和 CBD 在大鼠中的止恶心样作用（条件性张口）的潜力。此外，评估 DRN 内给予 CBD 产生止恶心样作用（并通过全身性 WAY100635 逆转）的能力。体外研究评估了 CBD 直接靶向 5-HT1A 受体的潜力，并改变 5-HT1A 激动剂 8-OH-DPAT 刺激大鼠脑干膜中[35S]GTPγS 结合的能力。
主要结果
CBD 抑制尼古丁、氯化锂（LiCl）和顺铂（20mg·kg-1，但不是 40mg·kg-1）诱导的 S. murinus 呕吐和 LiCl 诱导的条件性张口，在大鼠中。CBD 的止吐和止恶心样作用被 WAY100135 抑制，后者被 WAY100635 抑制。当给予 DRN 时：（i）WAY100635 逆转了全身 CBD 的止恶心样作用，（ii）CBD 抑制了恶心样作用，该作用被全身 WAY100635 逆转。CBD 还显示出显著的效力（在钟形剂量反应曲线中），增强了 8-OH-DPAT 刺激大鼠脑干膜中[35S]GTPγS 结合的能力。全身给予 CBD 和 8-OH-DPAT 协同抑制 LiCl 诱导的条件性张口。
结论和意义
这些结果表明，CBD 通过间接激活 DRN 中的 5-HT1A 自受体产生其止吐/止恶心作用。
相关文章
本文是关于大麻素在生物学和医学中的主题部分的一部分。要查看该部分中的其他文章，请访问 http://dx.doi.org/10.1111/bph.2012.165.section-8。要查看大麻素在生物学和医学中的第一部分，请访问 http://dx.doi.org/10.1111/bph.2011.163.section-7。
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