School of Psychology, Victoria University of Wellington, Wellington, New Zealand.
Psychopharmacology (Berl). 2012 Oct;223(4):389-99. doi: 10.1007/s00213-012-2726-9. Epub 2012 May 5.
Acute exposure to (±) 3, 4-methylenedioxymethamphetamine (MDMA) produces hyperlocomotion that is preferentially expressed in the periphery of closed chambers. Following repeated administration, however, a sensitized hyperlocomotor response is preferentially expressed in the center of an activity box, so that the response resembles the more generalized activity that is produced by D-amphetamine (AMPH).
The present study was designed to determine whether common neuroadaptations underlie the acute and sensitized responses to MDMA and AMPH.
Rats were pretreated with five daily injections of MDMA (10.0 mg/kg), AMPH (2.0 mg/kg), or saline. Following a 2-day drug-free period, dose-response curves for hyperactivity produced by MDMA (2.5-10.0 mg/kg), AMPH (0.5-2.0 mg/kg), SKF-81297 (1.0-2.0 mg/kg), or quinpirole (0.25-1.0 mg/kg) were obtained.
Effects of MDMA and AMPH were increased by pretreatment with both drugs. The sensitized response following MDMA exposure was preferentially expressed in the center compartment, but, following AMPH pretreatment, the sensitized response was observed in both compartments. Cross-sensitization was unidirectional; AMPH pretreatment failed to sensitize to the effects of MDMA, but MDMA pretreatment sensitized to the effects of AMPH. MDMA and AMPH pretreatment produced marginal increases in the effects of SKF-81297. The response to quinpirole was, however, greater following MDMA, but not AMPH, pretreatment.
These data suggest that repeated MDMA exposure produces sensitization via a unique neurochemical effect.
急性接触（±）3,4-亚甲基二氧甲基苯丙胺（MDMA）会产生过度活跃，这种过度活跃主要表现在封闭室的外围。然而，经过多次给药后，一种敏化的过度活跃反应会优先表现在活动箱的中心，使反应类似于由 D-苯丙胺（AMPH）产生的更广泛的活动。
本研究旨在确定急性和敏化反应 MDMA 和 AMPH 是否具有共同的神经适应机制。
大鼠预先用五剂 MDMA（10.0mg/kg）、AMPH（2.0mg/kg）或生理盐水处理。在 2 天无药期后，获得 MDMA（2.5-10.0mg/kg）、AMPH（0.5-2.0mg/kg）、SKF-81297（1.0-2.0mg/kg）或喹吡罗（0.25-1.0mg/kg）产生的过度活跃的剂量-反应曲线。
MDMA 和 AMPH 的作用都因两种药物的预处理而增加。MDMA 暴露后的敏化反应主要表现在中央隔室，但 AMPH 预处理后，敏化反应则表现在两个隔室。交叉敏化是单向的；AMPH 预处理不能敏化 MDMA 的作用，但 MDMA 预处理能敏化 AMPH 的作用。MDMA 和 AMPH 预处理对 SKF-81297 的作用仅有轻微的增加。然而，在 MDMA 预处理后，喹吡罗的反应更大，但在 AMPH 预处理后则不然。
这些数据表明，重复的 MDMA 暴露通过独特的神经化学作用产生敏化。
