Stanley N, Salem A, Irvine R J
Discipline of Pharmacology, School of Medical Sciences, Medical School North, University of Adelaide, Adelaide, South Australia 5005, Australia.
Neuroscience. 2007 Apr 25;146(1):321-9. doi: 10.1016/j.neuroscience.2007.01.012. Epub 2007 Feb 15.
We have recently demonstrated that co-administration of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") with the reversible monoamine oxidase type A (MAO-A) inhibitor moclobemide at an ambient temperature of 22 degrees C significantly increases striatal 5-HT outflow and 5-HT-mediated behaviors. In the present study, using microdialysis, we examined the effects of co-administration of MDMA or para-methoxyamphetamine (PMA) with moclobemide on striatal 5-HT outflow at the elevated ambient temperatures of 30 degrees C. Samples were collected every 30 min for 4 h and analyzed by high-performance liquid chromatography assay with electrochemical detection (HPLC-ED). 5-HT-mediated effects on body temperature and behavior were also recorded. Rats were treated with either saline or 20 mg/kg (i.p.) moclobemide, followed by 10 mg/kg (i.p.) MDMA, 10 mg/kg (i.p.) PMA or saline 60 min later. Both MDMA and PMA produced significant increases in 5-HT outflow (370% peak and 309% peak, respectively, P<0.05). MDMA and PMA significantly increased body temperature (+2.0 degrees C and +2.1 degrees C, respectively, P<0.01) and drug-related behaviors (P<0.05). When MDMA or PMA was co-administered with moclobemide, additional significant increases were seen in 5-HT outflow (850% peak, P<0.01 and 1450% peak, P<0.001, respectively) and only MDMA showed additional significant increase in body temperature (+5.0 degrees C, P<0.001). No additional increases were seen in behavioral activity. When moclobemide was co-administered with MDMA, sustained increases in body temperature were recorded that were significantly higher than with MDMA alone and such increases were not observed in our previous study at normal room temperature. Our results suggest greater risk of MDMA-induced adverse effects on body temperature regulation, compared with PMA, when used in combination with moclobemide at elevated ambient temperatures.
我们最近证明，在22摄氏度的环境温度下，将3,4-亚甲基二氧甲基苯丙胺（摇头丸，MDMA）与可逆性A型单胺氧化酶（MAO-A）抑制剂吗氯贝胺联合使用，可显著增加纹状体5-羟色胺（5-HT）的释放以及5-HT介导的行为。在本研究中，我们使用微透析技术，研究了在30摄氏度的较高环境温度下，将MDMA或对甲氧基苯丙胺（PMA）与吗氯贝胺联合使用对纹状体5-HT释放的影响。每隔30分钟采集一次样本，持续4小时，并通过高效液相色谱电化学检测法（HPLC-ED）进行分析。同时记录5-HT对体温和行为的影响。给大鼠腹腔注射生理盐水或20mg/kg吗氯贝胺，60分钟后再腹腔注射10mg/kg MDMA、10mg/kg PMA或生理盐水。MDMA和PMA均显著增加了5-HT的释放（峰值分别增加370%和309%，P<0.05）。MDMA和PMA显著提高了体温（分别升高2.0摄氏度和2.1摄氏度，P<0.01）以及与药物相关的行为（P<0.05）。当MDMA或PMA与吗氯贝胺联合使用时，5-HT的释放进一步显著增加（峰值分别增加850%，P<0.01和1450%，P<0.001），只有MDMA使体温进一步显著升高（升高5.0摄氏度，P<0.001）。行为活动未见进一步增加。当吗氯贝胺与MDMA联合使用时，记录到体温持续升高，且显著高于单独使用MDMA时，而在我们之前正常室温的研究中未观察到这种升高。我们的结果表明，在较高环境温度下与吗氯贝胺联合使用时，与PMA相比，MDMA对体温调节产生不良反应的风险更大。
