Balogh Brigitta, Molnar Eszter, Jakus Rita, Quate Linda, Olverman Henry J, Kelly Paul A T, Kantor Sandor, Bagdy Gyorgy
Laboratory of Neurochemistry and Experimental Medicine and Department of Vascular Neurology, Semmelweis University, National Institute of Psychiatry and Neurology, Huvosvolgyi ut 116, 1021 Budapest, Hungary.
Psychopharmacology (Berl). 2004 May;173(3-4):296-309. doi: 10.1007/s00213-004-1787-9. Epub 2004 Apr 9.
Despite the well documented neurochemical actions of 3,4-methylenedioxymethamphetamine (MDMA), acute effects in rats previously exposed to the drug have not been extensively explored.
To examine motor activity and vigilance effects of MDMA in drug-naive rats and in rats exposed to the drug 3 weeks earlier.
MDMA (15 mg/kg, i.p.) was administered to Dark Agouti rats. Motor activity, wakefulness, light slow wave sleep (SWS-1), deep slow wave sleep (SWS-2) and paradoxical sleep (PS), sleep and PS latencies were measured. Acrophases and amplitudes of the 24 h cycles were calculated by cosinor analysis. In parallel groups, local cerebral glucose utilization (lCMRglu) and (3H)-paroxetine binding were measured in motor areas of the brain.
In drug-naive rats MDMA caused marked increases in motor activity and wakefulness for at least 5-6 h. Circadian patterns of motor activity and sleep/vigilance parameters were altered up to 5 days after treatment. Despite most parameters tending to return to normal, there were still significant effects of MDMA on motor activity, wakefulness, and SWS-2 28 days later. Acute MDMA administration caused significant increases in lCMRglu, but after 3 weeks lCMRglu was decreased in the same brain areas. No significant change in [3H]paroxetine binding was observed in motor areas, although significant reductions were seen elsewhere (neocortex -81%). In rats exposed to MDMA 3 weeks earlier, most acute effects induced by MDMA administration were similar to those in drug-naive rats, but shorter duration of the acute effects were found in motor activity and vigilance.
Our findings provide evidence that MDMA use can lead to long-term changes in regulation of circadian rhythms, motor activity and sleep generation.
尽管3,4-亚甲基二氧甲基苯丙胺（摇头丸）的神经化学作用已有充分记录，但此前接触过该药物的大鼠的急性效应尚未得到广泛研究。
研究摇头丸对未接触过药物的大鼠以及3周前接触过该药物的大鼠的运动活动和警觉性影响。
对深色刺豚鼠腹腔注射摇头丸（15毫克/千克）。测量运动活动、清醒状态、浅慢波睡眠（SWS-1）、深慢波睡眠（SWS-2）和异相睡眠（PS）、睡眠和PS潜伏期。通过余弦分析计算24小时周期的峰相位和振幅。在平行组中，测量大脑运动区域的局部脑葡萄糖利用率（lCMRglu）和（3H）-帕罗西汀结合情况。
在未接触过药物的大鼠中，摇头丸导致运动活动和清醒状态显著增加至少5-6小时。治疗后长达5天，运动活动以及睡眠/警觉参数的昼夜节律模式发生改变。尽管大多数参数趋于恢复正常，但28天后摇头丸对运动活动、清醒状态和SWS-2仍有显著影响。急性给予摇头丸导致lCMRglu显著增加，但3周后同一脑区的lCMRglu降低。在运动区域未观察到[3H]帕罗西汀结合有显著变化，尽管在其他部位（新皮层 -81%）有显著降低。在3周前接触过摇头丸的大鼠中，给予摇头丸引起的大多数急性效应与未接触过药物的大鼠相似，但运动活动和警觉性方面的急性效应持续时间较短。
我们的研究结果提供了证据，表明使用摇头丸可导致昼夜节律、运动活动和睡眠产生调节的长期变化。
