University of Tuebingen, Neuropharmacology, Auf der Morgenstelle 28E, Tuebingen, Germany.
Addict Biol. 2010 Jan;15(1):35-44. doi: 10.1111/j.1369-1600.2009.00187.x.
Despite the great popularity of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) as a drug of abuse, not much is known about the detailed mechanisms of the acute and subchronic effects of the drug. There is especially a lack of information about the distinct behavioural effects of its optical isomers (enantiomers) R- and S-MDMA compared with the racemic RS-MDMA. For this purpose, adolescent rats were repetitively treated during two treatment stages (stage 1: days 1-10; stage 2: days 15, 17, 19) with RS-MDMA (5 or 10 mg/kg) or each of the respective enantiomers (5 mg/kg). The repeated treatment started on postnatal day (PND) 32 and locomotor activity was measured on each day by means of a photobeam-equipped activity box system. RS-MDMA or S-MDMA administration led acutely to massive hyperlocomotion and subchronically, to the development of behavioural sensitization after a short habituation period. R-MDMA was free of hyperactivating effects and even decreased locomotor behaviour upon repeated treatment. Nevertheless, co-administration of R-MDMA increased the hyperactivity of S-MDMA and made the S-MDMA induced behavioural sensitization state-dependent. The animals pre-treated with R-MDMA showed a sensitized response in adulthood when tested with RS-MDMA. Our results indicated that even in the absence of substantial neurotoxicity, both MDMA enantiomers can lead to long-term changes in brain circuitry and concomitant behavioural changes when repeatedly administered in adolescence. The sensitization development was most pronounced in the animals treated with S- and RS-MDMA; the animals with R-MDMA did not develop sensitization under repeated treatment but expressed a sensitized response when challenged with RS-MDMA.
尽管 3,4-亚甲二氧基甲基苯丙胺（MDMA，摇头丸）作为滥用药物非常流行，但人们对其急性和亚慢性作用的详细机制知之甚少。特别是，与外消旋 RS-MDMA 相比，其光学异构体（对映异构体）R-和 S-MDMA 的独特行为效应的信息尤其缺乏。为此，青少年大鼠在两个治疗阶段（阶段 1：第 1-10 天；阶段 2：第 15、17、19 天）中反复接受 RS-MDMA（5 或 10mg/kg）或各自的对映异构体（5mg/kg）的治疗。重复治疗从出生后第 32 天开始，通过配备光电束的活动箱系统每天测量运动活动。RS-MDMA 或 S-MDMA 给药急性导致大量多动，亚慢性导致短暂适应期后出现行为敏化。R-MDMA 没有激活作用，甚至在反复治疗后降低运动行为。然而，R-MDMA 的共同给药增加了 S-MDMA 的过度活跃，并使 S-MDMA 诱导的行为敏化状态依赖。用 R-MDMA 预处理的动物在成年期用 RS-MDMA 测试时表现出敏化反应。我们的结果表明，即使没有实质性的神经毒性，两种 MDMA 对映体在青春期反复给药时也会导致大脑回路的长期变化和伴随的行为变化。在接受 S-和 RS-MDMA 治疗的动物中，敏化发展最为明显；用 R-MDMA 治疗的动物在反复治疗下不会产生敏化，但用 RS-MDMA 挑战时会表现出敏化反应。
