Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida, USA.
Department of Medicine, School of Medicine, University of Atacama, Copiapó, Chile.
Addict Biol. 2022 Sep;27(5):e13223. doi: 10.1111/adb.13223.
The use of areca nuts (areca) in the form of betel quids constitutes the fourth most common addiction in the world, associated with high risk for oral disease and cancer. Areca is a complex natural product, making it difficult to identify specific components associated with the addictive and carcinogenic properties. It is commonly believed that the muscarinic agonist arecoline is at the core of the addiction. However, muscarinic receptor activation is not generally believed to support drug-taking behaviour. Subjective accounts of areca use include descriptions of both sedative and stimulatory effects, consistent with the presence of multiple psychoactive agents. We have previously reported partial agonism of α4-containing nicotinic acetylcholine receptors by arecoline and subsequent inhibition of those receptors by whole areca broth. In the present study, we report the inhibition of nicotinic acetylcholine receptors and other types of neurotransmitter receptors with compounds of high molecular weight in areca and the ability of low molecular weight areca extract to activate GABA and glutamate receptors. We confirm the presence of a high concentration of GABA and glutamate in areca. Additionally, data also indicate the presence of a dopamine and serotonin transporter blocking activity in areca that could account for the reported stimulant and antidepressant activity. Our data suggest that toxic elements of high molecular weight may contribute to the oral health liability of betel quid use, while two distinct low molecular weight components may provide elements of reward, and the nicotinic activity of arecoline contributes to the physical dependence of addiction.
槟榔果(槟榔)以咀嚼块的形式被使用,是世界范围内第四大常见的成瘾物质,与口腔疾病和癌症的高风险密切相关。槟榔是一种复杂的天然产物,这使得确定与成瘾性和致癌性相关的特定成分变得困难。人们普遍认为,毒蕈碱激动剂槟榔碱是成瘾的核心。然而,毒蕈碱受体的激活通常不被认为支持药物滥用行为。关于槟榔使用的主观描述包括镇静和刺激作用的描述,这与多种精神活性物质的存在一致。我们之前曾报道过槟榔碱对含有α4 的烟碱型乙酰胆碱受体的部分激动作用,以及随后全槟榔汤对这些受体的抑制作用。在本研究中,我们报告了槟榔中具有高分子量的化合物对烟碱型乙酰胆碱受体和其他类型神经递质受体的抑制作用,以及低分子量槟榔提取物对 GABA 和谷氨酸受体的激活作用。我们证实了槟榔中存在高浓度的 GABA 和谷氨酸。此外,数据还表明槟榔中存在多巴胺和 5-羟色胺转运体阻断活性,这可能解释了报告中的兴奋剂和抗抑郁活性。我们的数据表明,高分子量的有毒元素可能导致咀嚼槟榔与口腔健康不良有关,而两种不同的低分子量成分可能提供奖赏元素,并且槟榔碱的烟碱活性有助于成瘾的身体依赖。