Clemens Kelly J, Van Nieuwenhuyzen Petra S, Li Kong M, Cornish Jennifer L, Hunt Glenn E, McGregor Iain S
School of Psychology, University of Sydney, 2006 Sydney, NSW, Australia.
Psychopharmacology (Berl). 2004 May;173(3-4):318-25. doi: 10.1007/s00213-004-1786-x. Epub 2004 Mar 17.
3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) are illicit drugs that are increasingly used in combination. The acute and long-term effects of MDMA/METH combinations are largely uncharacterised.
The current study investigated the behavioural, thermal and neurotoxic effects of MDMA and METH when given alone or in combined low doses.
Male rats received four injections, one every 2 h, of vehicle, MDMA (2.5 or 5 mg/kg per injection), METH (2.5 or 5 mg/kg per injection) or combined MDMA/METH (1.25+1.25 mg/kg per injection or 2+2 mg/kg per injection). Drugs were given at an ambient temperature of 28 degrees C to simulate hot nightclub conditions. Body temperature, locomotor activity and head-weaving were assessed during acute drug administration while social interaction, anxiety-related behavior on the emergence test and neurochemical parameters were assessed 4-7 weeks later.
All treatments acutely increased locomotor activity, while pronounced head-weaving was seen with both MDMA/METH treatments and the higher dose METH treatment. Acute hyperthermia was greatest with the higher dose MDMA/METH treatment and was also seen with MDMA but not METH treatment. Several weeks after drug administration, both MDMA/METH groups, both METH groups and the higher dose MDMA group showed decreased social interaction relative to controls, while both MDMA/METH groups and the lower dose MDMA group showed increased anxiety-like behaviour on the emergence test. MDMA treatment caused 5-HT and 5-HIAA depletion in several brain regions, while METH treatment reduced dopamine in the prefrontal cortex. Combined MDMA/METH treatment caused 5-HT and 5-HIAA depletion in several brain regions and a unique depletion of dopamine and DOPAC in the striatum.
These results suggest that MDMA and METH in combination may have greater adverse acute effects (head-weaving, body temperature) and long-term effects (decreased social interaction, increased emergence anxiety, dopamine depletion) than equivalent doses of either drug alone.
3,4-亚甲基二氧甲基苯丙胺（摇头丸）和甲基苯丙胺（冰毒）是越来越常被混合使用的非法药物。摇头丸/冰毒组合的急性和长期影响在很大程度上尚未明确。
本研究调查了单独或低剂量联合使用摇头丸和冰毒时的行为、热效应和神经毒性作用。
雄性大鼠每隔2小时接受4次注射，分别注射溶剂、摇头丸（每次注射2.5或5毫克/千克）、冰毒（每次注射2.5或5毫克/千克）或联合使用摇头丸/冰毒（每次注射1.25 + 1.25毫克/千克或2 + 2毫克/千克）。在28摄氏度的环境温度下给药，以模拟炎热的夜总会环境。在急性给药期间评估体温、运动活动和头部摆动情况，而在4至7周后评估社交互动、出箱试验中与焦虑相关的行为以及神经化学参数。
所有处理均急性增加运动活动，而摇头丸/冰毒处理组和高剂量冰毒处理组均出现明显的头部摆动。高剂量摇头丸/冰毒处理组的急性体温过高最为明显，摇头丸处理组也出现这种情况，但冰毒处理组未出现。给药数周后，与对照组相比，摇头丸/冰毒组、冰毒组和高剂量摇头丸组的社交互动均减少，而摇头丸/冰毒组和低剂量摇头丸组在出箱试验中出现类似焦虑行为增加。摇头丸处理导致几个脑区的5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）耗竭，而冰毒处理降低了前额叶皮质中的多巴胺。联合使用摇头丸/冰毒处理导致几个脑区的5-HT和5-HIAA耗竭，并使纹状体中的多巴胺和3,4-二羟基苯乙酸（DOPAC）出现独特的耗竭。
这些结果表明，与单独使用等量的任何一种药物相比，摇头丸和冰毒联合使用可能具有更大的急性不良影响（头部摆动、体温）和长期影响（社交互动减少、出箱焦虑增加、多巴胺耗竭）。
