Increased anxiety and 'depressive' symptoms months after MDMA ('ecstasy') in rats: drug-induced hyperthermia does not predict long-term outcomes
Increased anxiety and 'depressive' symptoms months after MDMA ('ecstasy') in rats: drug-induced hyperthermia does not predict long-term outcomes
复制标题
DOI：
10.1007/s00213-003-1452-8
复制
发表时间：
2003-08-01
影响因子：
3.4
通讯作者：
Hunt, GE
中科院分区：
文献类型：
--
作者：
McGregor, IS;Gurtman, CG;Hunt, GE
理由。在确定对大脑5-羟色胺系统的长期神经毒性作用以及相关的情绪和行为变化方面，是否由MDMA（摇头丸）引起的急性高热起着重要作用，这一点还不确定。Objective.本研究评估了在MDMA处理的大鼠中观察到的长期行为和认知变化是否受到给药时体温过高的影响。法雄性Wistar大鼠在高环境温度（28 ℃）或低环境温度（16 ℃）下接受MDMA（4 × 5 mg/kg i. p.，持续4小时，连续2天）或溶剂处理。8至18周后，对大鼠进行焦虑行为测量（社交互动和出现测试），认知测试（物体识别测试）和强迫游泳抑郁测试。在行为测试结束时，处死大鼠，并使用HPLC分析其大脑。结果MDMA治疗引起明显和一致的体温升高（28 ℃）和体温降低（16 ℃）。几个月后，在16 ℃或28 ℃下用MDMA预处理的大鼠在社会互动和出现测试中表现出焦虑增加，在强迫游泳测试中逃跑尝试减少，不动性增加。MDMA预处理也与物体识别测试中记忆力较差有关，但仅限于在28摄氏度下给予该药物的大鼠。无论给药时的体温如何，用MDMA预处理的大鼠的海马、纹状体、杏仁核和皮质中的5-HT均出现损失。然而，在28 ℃预处理的大鼠中，杏仁核和海马体中的5-HIAA损失更大。在服用摇头丸的大鼠中，纹状体中的多巴胺也被耗尽。结论.这些结果表明，在MDMA给药时的高温是没有必要产生随后的5-HT耗竭和焦虑的大鼠。他们还扩展了先前在大鼠中短暂暴露于MDMA的长期影响的发现，以包括强迫游泳模型中明显的“抑郁”症状。
Rationale. There is some uncertainty whether the acute hyperthermia caused by MDMA (ecstasy) plays a significant role in determining the long-term neurotoxic effects on brain 5-HT systems and associated changes in mood and behaviour. Objective. The present study assessed whether long-term behavioural and cognitive changes seen in MDMA-treated rats are affected by hyperthermia at the time of drug administration. Method. Male Wistar rats were treated with MDMA (4x5 mg/kg i.p. over 4 h on 2 consecutive days) or vehicle at either a high ambient temperature (28degreesC) or a low ambient temperature (16degreesC). Eight to 18 weeks later, rats were tested in behavioural measures of anxiety (social interaction and emergence tests), a test of cognition (object recognition test) and the forced swim test of depression. At the conclusion of behavioural testing the rats were killed and their brains analysed using HPLC. Results. MDMA treatment caused a clear and consistent hyperthermia at 28degreesC and hypothermia at 16degreesC. Months later, rats pre-treated with MDMA at either 16 or 28degreesC displayed increased anxiety in the social interaction and emergence tests and reduced escape attempts and increased immobility in the forced swim test. MDMA pre-treatment was also associated with poorer memory on the object recognition test, but only in rats given the drug at 28degreesC. Rats pre-treated with MDMA showed loss of 5-HT in the hippocampus, striatum, amygdala and cortex, regardless of body temperature at the time of dosing. However, 5-HIAA loss in the amygdala and hippocampus was greater in rats pre-treated at 28degreesC. Dopamine in the striatum was also depleted in rats given MDMA. Conclusions. These results indicate that hyperthermia at the time of dosing with MDMA is not necessary to produce subsequent 5-HT depletion and anxiety in rats. They also extend previous findings of long-term effects of brief exposure to MDMA in rats to include apparent 'depressive' symptoms in the forced swim model.