生物谷綜合：2007年56卷第6期《神經(jīng)元》的封面是幾條金魚在背景為大麻葉的花瓶中漫游的蒙太奇照片。這張照片對應(yīng)的文章是Cachope等報道的關(guān)于大麻中的成分內(nèi)大麻素具有介導(dǎo)增強(qiáng)突觸傳遞作用的研究,。
此前的研究表明,，大麻醇I型受體的突觸前激活作用表明大麻中的內(nèi)大麻素是突觸傳遞的化學(xué)抑制劑。然而,，Cachope小組的研究結(jié)果否認(rèn)了這一觀點(diǎn),，他們發(fā)現(xiàn)內(nèi)大麻素的分散釋放能夠從電與化學(xué)兩方面混合增強(qiáng)Mauthner金魚細(xì)胞的突觸傳遞。
更值得注意的是,，這種增強(qiáng)作用并非只限于突觸響應(yīng)的谷氨酸鹽成分,，而且還包括相應(yīng)的電傳遞的增強(qiáng)。研究表明,，這種作用涉及大麻醇I型受體的活化,，以及通過附近的靜脈曲張釋放多巴胺進(jìn)行間接介導(dǎo)，接著再通過環(huán)磷酸腺苷依賴型蛋白激酶介導(dǎo)突觸的方式增強(qiáng)突觸反應(yīng),。因此,，內(nèi)大麻素的釋放具有明顯增強(qiáng)突觸傳遞的作用，其功能包括調(diào)節(jié)間隙連接介導(dǎo)電突觸。
研究人員認(rèn)為,，類似的內(nèi)大麻素與多巴胺系統(tǒng)的相互作用可能分布廣泛,，而其它大麻衍生物的潛在作用也值得進(jìn)一步研究。（武彥文/編譯）
原始出處：
Neuron, Vol 56, 1034-1047, 20 December 2007
Article
Potentiation of Electrical and Chemical Synaptic Transmission Mediated by Endocannabinoids
Roger Cachope,1 Ken Mackie,2 Antoine Triller,3 John O'Brien,4 and Alberto E. Pereda1,
1 Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA
2 Department of Anesthesiology, University of Washington, Seattle, WA 98195, USA
3 Ecole Normale Superieure, Paris, France
4 University of Texas Health Science Center, Houston, TX 77030, USA
Corresponding author
Alberto E. Pereda
[email protected]
Summary
Endocannabinoids are well established as inhibitors of chemical synaptic transmission via presynaptic activation of the cannabinoid type 1 receptor (CB1R). Contrasting this notion, we show that dendritic release of endocannabinoids mediates potentiation of synaptic transmission at mixed (electrical and chemical) synaptic contacts on the goldfish Mauthner cell. Remarkably, the observed enhancement was not restricted to the glutamatergic component of the synaptic response but also included a parallel increase in electrical transmission. This effect involved the activation of CB1 receptors and was indirectly mediated via the release of dopamine from nearby varicosities, which in turn led to potentiation of the synaptic response via a cAMP-dependent protein kinase-mediated postsynaptic mechanism. Thus, endocannabinoid release can potentiate synaptic transmission, and its functional roles include the regulation of gap junction-mediated electrical synapses. Similar interactions between endocannabinoid and dopaminergic systems may be widespread and potentially relevant for the motor and rewarding effects of cannabis derivatives.
