Vorhees Charles V, Reed Tracy M, Skelton Matthew R, Williams Michael T
Division of Developmental Biology (MLC 7007), Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA.
Int J Dev Neurosci. 2004 Aug-Oct;22(5-6):247-59. doi: 10.1016/j.ijdevneu.2004.06.003.
3,4-methylenedioxymethamphetamine (MDMA) in previous experiments has been shown to induce long-term spatial and sequential learning and memory deficits in adult offspring after exposure to the drug on postnatal (P) days 11-20, but not after exposure on P1-10. Herein we further tested for the effects of MDMA (0, 5, 10 or 20 mg/kg x 2/day) after exposure on P11-20 on reference and working memory in the Morris water maze (MWM), on reference memory in the Barnes maze, and on cued learning in the visible platform version of the MWM. The MWM and Barnes mazes were counterbalanced such that half the litters received the MWM-first and the other half received the Barnes maze first. Effects on MWM performance as a function of test order were observed. For animals that received the Barnes maze first, spatial MWM learning and memory trends were seen but they were not significantly different between MDMA groups and saline controls. For those receiving the MWM-first, there are consistent impairments on all measures in the MDMA groups compared to controls on MWM performance (latency, path length, and cumulative distance from the goal). On probe trials, MDMA animals receiving the MWM-first showed increased distance from the target site compared to controls. There were no MDMA effects seen on cued trials in the MWM or on straight channel swimming trials regardless of test order, indicating that MDMA had no effects on swimming ability or on the skills needed to learn the MWM. Similarly, there were no effects of MDMA on MWM working memory regardless of test order. No MDMA effects on the Barnes maze were found regardless of test order, however, the interpretation of this finding was compromised by the poor performance of the animals on this task.
在先前的实验中，已表明3,4-亚甲基二氧甲基苯丙胺（MDMA）在产后（P）第11 - 20天给成年后代暴露于该药物后会诱导长期的空间和序列学习及记忆缺陷，但在P1 - 10天暴露后则不会。在此，我们进一步测试了MDMA（0、5、10或20毫克/千克×2/天）在P11 - 20天暴露后对莫里斯水迷宫（MWM）中的参考记忆和工作记忆、巴恩斯迷宫中的参考记忆以及MWM可见平台版本中的线索学习的影响。MWM和巴恩斯迷宫进行了平衡处理，使得一半的窝仔先接受MWM测试，另一半先接受巴恩斯迷宫测试。观察到了测试顺序对MWM性能的影响。对于先接受巴恩斯迷宫测试的动物，观察到了空间MWM学习和记忆趋势，但MDMA组和生理盐水对照组之间没有显著差异。对于先接受MWM测试的动物，与对照组相比，MDMA组在MWM性能的所有指标（潜伏期、路径长度和距目标的累积距离）上均存在持续损伤。在探测试验中，先接受MWM测试的MDMA动物与对照组相比，距目标位点的距离增加。无论测试顺序如何，在MWM的线索试验或直通道游泳试验中均未观察到MDMA的影响，这表明MDMA对游泳能力或学习MWM所需的技能没有影响。同样，无论测试顺序如何，MDMA对MWM工作记忆均无影响。无论测试顺序如何，均未发现MDMA对巴恩斯迷宫有影响，然而，由于动物在该任务上表现不佳，这一发现的解释受到了影响。
