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9-四氢大麻酚可诱导人纹状体中多巴胺的释放。

Delta 9-tetrahydrocannabinol induces dopamine release in the human striatum.

作者信息

Bossong Matthijs G, van Berckel Bart N M, Boellaard Ronald, Zuurman Lineke, Schuit Robert C, Windhorst Albert D, van Gerven Joop M A, Ramsey Nick F, Lammertsma Adriaan A, Kahn René S

机构信息

Department of Neurology and Neurosurgery, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.

出版信息

Neuropsychopharmacology. 2009 Feb;34(3):759-66. doi: 10.1038/npp.2008.138. Epub 2008 Aug 27.

Abstract

The influence of cannabis on mental health receives growing scientific and political attention. An increasing demand for treatment of cannabis dependence has refueled the discussion about the addictive potential of cannabis. A key feature of all addictive drugs is the ability to increase synaptic dopamine levels in the striatum, a mechanism involved in their rewarding and motivating effects. However, it is currently unknown if cannabis can stimulate striatal dopamine neurotransmission in humans. Here we show that Delta 9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, induces dopamine release in the human striatum. Using the dopamine D(2)/D(3) receptor tracer [(11)C]raclopride and positron emission tomography in seven healthy subjects, we demonstrate that THC inhalation reduces [(11)C]raclopride binding in the ventral striatum and the precommissural dorsal putamen but not in other striatal subregions. This is consistent with an increase in dopamine levels in these regions. These results suggest that THC shares a potentially addictive property with other drugs of abuse. Further, it implies that the endogenous cannabinoid system is involved in regulating striatal dopamine release. This allows new directions in research on the effects of THC in neuropsychiatric disorders, such as schizophrenia.

摘要

大麻对心理健康的影响受到了越来越多的科学和政治关注。对大麻依赖治疗的需求不断增加,这再次引发了关于大麻成瘾潜力的讨论。所有成瘾性药物的一个关键特征是能够提高纹状体中的突触多巴胺水平,这一机制与其奖赏和激励作用有关。然而,目前尚不清楚大麻是否能刺激人类纹状体中的多巴胺神经传递。在此我们表明,大麻中的主要精神活性成分Δ9 - 四氢大麻酚(THC)可诱导人类纹状体中的多巴胺释放。在七名健康受试者中,我们使用多巴胺D(2)/D(3)受体示踪剂[(11)C]雷氯必利和正电子发射断层扫描技术,证明吸入THC可降低腹侧纹状体和连合前背侧壳核中的[(11)C]雷氯必利结合,但在其他纹状体亚区域则不然。这与这些区域中多巴胺水平的升高相一致。这些结果表明,THC与其他滥用药物具有潜在的成瘾特性。此外,这意味着内源性大麻素系统参与调节纹状体多巴胺释放。这为研究THC在神经精神疾病(如精神分裂症)中的作用开辟了新的方向。

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