Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, United States.
Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, 40292, United States.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):1366-1370. doi: 10.1016/j.bbrc.2020.10.021. Epub 2020 Oct 21.
Nematode Caenorhabditis elegans (C. elegans) exhibited a vigorous swimming behavior in liquid medium. Addition of dopamine inhibited the swimming behavior, causing paralysis in 65% of wild-type nematodes. Interestingly, phytocannabinoids cannabidiol (CBD) or cannabidivarin (CBDV), caused paralysis in 40% of the animals. Knockout of DOP-3, the dopamine D2-like receptor critical for locomotor behavior, eliminated the paralysis induced by dopamine, CBD, and CBDV. In contrast, both CBD and CBDV caused paralysis in animals lacking CAT-2, an enzyme necessary for dopamine synthesis. Co-administration of dopamine with either CBD or CBDV caused paralysis similar to that of either phytocannabinoid treatment alone. These data support the notion that CBD and CBDV act as functional partial agonists on dopamine D2-like receptors in vivo. The discovery that dopamine receptor is involved in the actions of phytocannabinoids moves a significant step toward our understanding of the mechanisms for medical uses of cannabis in the treatment of neurological and psychiatric disorders.
秀丽隐杆线虫（C. elegans）在液体介质中表现出活跃的游动行为。添加多巴胺会抑制游动行为，导致 65%的野生型线虫瘫痪。有趣的是，植物大麻素大麻二酚（CBD）或大麻素（CBDV）会导致 40%的动物瘫痪。DOP-3 的敲除，即对运动行为至关重要的多巴胺 D2 样受体，消除了多巴胺、CBD 和 CBDV 引起的瘫痪。相比之下，缺乏多巴胺合成所必需的酶 CAT-2 的动物，CBD 和 CBDV 都会导致其瘫痪。多巴胺与 CBD 或 CBDV 联合给药会导致与单独使用植物大麻素治疗相似的瘫痪。这些数据支持 CBD 和 CBDV 在体内作为多巴胺 D2 样受体的功能性部分激动剂的观点。发现多巴胺受体参与植物大麻素的作用，这是朝着理解大麻在治疗神经和精神疾病方面的医学用途的机制迈出的重要一步。
