Yusoff Nurul H M, Suhaimi Farah W, Vadivelu Raja K, Hassan Zurina, Rümler Anne, Rotter Andrea, Amato Davide, Dringenberg Hans C, Mansor Sharif M, Navaratnam Visweswaran, Müller Christian P
Centre for Drug Research, Universiti Sains Malaysia, Malaysia.
Eskitis Institute for Drug Discovery, Griffith University, Australia.
Addict Biol. 2016 Jan;21(1):98-110. doi: 10.1111/adb.12185. Epub 2014 Sep 28.
Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug.
帽柱木碱是植物 kratom/ketum 中的主要精神活性生物碱。Kratom 在东南亚被广泛用作消遣性毒品，并且在西方世界越来越多地以纯化合物或“草本兴奋剂”制剂成分的形式出现。虽然帽柱木碱/kratom 可能具有镇痛、肌肉松弛和抗炎作用，但其成瘾特性以及对认知表现的影响尚不清楚。我们从该植物中分离出帽柱木碱，并对其在大鼠和小鼠中的行为效应进行了全面研究。在此，我们描述了急性和慢性给予帽柱木碱后的成瘾特征和认知障碍，这与吗啡的情况极为相似。急性给予帽柱木碱对运动活动有复杂影响。重复给药会诱导运动敏化、抗焦虑作用和条件性位置偏爱，增强中脑多巴胺转运体和多巴胺受体调节因子 mRNA 的表达。虽然在戒断期间自发运动活动没有增加，但动物在长达 14 天的时间里对小剂量的激发刺激表现出超敏反应。戒断 12 小时后出现严重的躯体戒断症状，戒断 24 小时后焦虑水平升高变得明显。急性给予帽柱木碱会独立损害被动回避学习、记忆巩固和提取，这可能是由皮质振荡活动的破坏介导的，包括脑电图中低频节律（δ波和θ波）的抑制。慢性给予帽柱木碱会导致被动回避和物体识别学习受损。总之，这些发现为帽柱木碱具有成瘾潜力并伴有认知障碍提供了证据，这表明应将其归类为有害药物。
