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首页> 外文期刊>Addiction biology >Effects of repeated treatment with MDMA on working memory and behavioural flexibility in mice.
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Effects of repeated treatment with MDMA on working memory and behavioural flexibility in mice.

机译：用MDMA重复治疗对小鼠的工作记忆和行为灵活性的影响。

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Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) produces dopaminergic neurotoxicity in mice. However, it is still not clear whether this exposure induces deficits in cognitive processing related to specific subsets of executive functioning. We evaluated the effects of neurotoxic and non-neurotoxic doses of MDMA (0, 3 and 30?mg/kg, twice daily for 4?days) on working memory and attentional set-shifting in mice, and changes in extracellular levels of dopamine (DA) in the striatum. Treatment with MDMA (30?mg/kg) disrupted performance of acquired operant alternation, and this impairment was still apparent 5?days after the last drug administration. Decreased alternation was not related to anhedonia because no differences were observed between groups in the saccharin preference test under similar experimental conditions. Correct responding on delayed alternation was increased 1?day after repeated treatment with MDMA (30?mg/kg), probably because of general behavioural quiescence. Notably, the high dose regimen of MDMA impaired attentional set-shifting related to an increase in total perseveration errors. Finally, basal extracellular levels of DA in the striatum were not modified in mice repeatedly treated with MDMA with respect to controls. However, an acute challenge with MDMA (10?mg/kg) failed to increase DA outflow in mice receiving the highest MDMA dose (30?mg/kg), corroborating a decrease in the functionality of DA transporters. Seven days after this treatment, the effects of MDMA on DA outflow were recovered. These results suggest that repeated neurotoxic doses of MDMA produce lasting impairments in recall of alternation behaviour and reduce cognitive flexibility in mice.
机译：重复施用3,4-亚甲二氧基甲基苯丙胺（MDMA）在小鼠中产生多巴胺能神经毒性。然而，目前尚不清楚这种暴露是否会引起与执行功能的特定子集有关的认知加工缺陷。我们评估了神经毒性和非神经毒性剂量的摇头丸（0、3和30？mg / kg，每天两次，共4天）对小鼠的工作记忆和注意力转移的影响以及细胞外多巴胺水平的变化（ DA）在纹状体中。用MDMA（30？mg / kg）进行的治疗破坏了获得性手术交替的表现，这种损害在最后一次给药后5天仍然很明显。交替减少与快感缺失无关，因为在相似的实验条件下，糖精偏爱试验的各组之间未观察到差异。 MDMA（30？mg / kg）重复治疗后1天，对延迟交替的正确反应增加了，这可能是由于一般的行为静止所致。值得注意的是，高剂量的MDMA方案损害了注意力的集中转移，这与总持续性错误的增加有关。最后，相对于对照，在用MDMA反复治疗的小鼠中，纹状体中DA的基础细胞外水平没有改变。但是，对MDMA（10？mg / kg）的急性攻击未能增加接受最高MDMA剂量（30？mg / kg）的小鼠的DA流出，证实了DA转运蛋白的功能降低。处理后7天，MDMA对DA流出的影响得以恢复。这些结果表明重复的神经毒性剂量的MDMA会在交替行为的回忆中产生持久的损伤，并降低小鼠的认知灵活性。

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