Acute effects of dexfenfluramine (d-FEN) and methylenedioxymethamphetamine (MDMA) before and after short-course, high-dose treatment
Acute effects of dexfenfluramine (d-FEN) and methylenedioxymethamphetamine (MDMA) before and after short-course, high-dose treatment
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DOI：
10.1111/j.1749-6632.1998.tb08233.x
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发表时间：
1998-01-01
期刊：
影响因子：
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通讯作者：
Paule, MG
中科院分区：
文献类型：
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作者：
Frederick, DL;Ali, SF;Paule, MG
另外三只动物作为神经化学终点的对照。OTB由五个食物强化任务组成，旨在模拟学习、短期记忆和注意力、时间估计、动机、颜色和位置歧视等方面。在每种药物的急性作用确定后不久，其中三只猴子接受了短疗程的高剂量暴露（2次/天x 4天，肌肉注射）MDMA（10毫克/公斤），而三只猴子暴露于相同方案的d-FEN（5毫克/公斤）。大约一个月后，每种药物的急性效应再次确定，在暴露于高剂量d-FEN的猴子中，OTB任务对MDMA或d-FEN急性中断的敏感性基本不变。相反，用大剂量MDMA治疗的猴子对两种药物的急性行为影响不太敏感，尽管这种影响在d-FEN中更为常见，并且是针对OTB任务的。因此，高剂量MDMA暴露后发现了MDMA和d-FEN对急性行为影响的残余行为耐受，而高剂量d-FEN暴露后则没有。这些发现令人惊讶，因为在短期高剂量MDMA或d-FEN治疗大约6个月后，在所有猴子中观察到类似的神经化学效应（即额叶皮层和海马体中血清素显著减少约50%）。
The acute behavioral effects of methylenedioxymethamphetamine (MDMA) and dexfenfluramine (d-FEN) sere assessed in six rhesus monkeys using performance in the National Center for Toxicological Research (NCTR) Operant Test Battery (OTB); three additional animals served as controls for neurochemical endpoints. The OTB consists of five food-reinforced tasks designed to model aspects of learning, shortterm memory and attention, time estimation, motivation, and color and position discrimination. Shortly after the acute effects of each drug were determined, three of the monkeys received a short-course, high-dose exposure (2x/day x 4 days, intramuscular (i.m.) injections) of MDMA (10 mg/kg), while three monkeys were exposed to an identical regimen of d-FEN (5 mg/kg). Approximately one month later, the acute effects of each drug sere again determined, In monkeys exposed to high-dose d-FEN, the sensitivities of the OTB tasks to acute disruption by either MDMA or d-FEN were essentially unchanged. Conversely, monkeys treated with high-dose MDMA were less sensitive to the acute behavioral effects of both drugs, although such an effect was seen more frequently for d-FEN and was OTB task specific. Thus a residual behavioral tolerance to the acute behavioral effects of MDMA and d-FEN was noted after high-dose MDMA exposure, but not after high-dose d-FEN exposure. These findings are surprising, as similar neurochemical effects (i.e., significant decreases of ca, 50% in serotonin in frontal cortex and hippocampus) were observed in all monkeys approximately six months after short-course, high-dose MDMA or d-FEN treatment.