Biopsychology & Comparative Neuroscience, ICBiBE, University of Valencia-FGUV & Red de Trastornos Adictivos, RETICS, Spain.
Addict Biol. 2010 Oct;15(4):413-23. doi: 10.1111/j.1369-1600.2010.00259.x.
Recent trend assessments of drug consumption reveal an increase in the simultaneous use of several drugs at raves, clubs and college settings among youngsters and young adults. We studied in adolescent rats the effects of repeated exposure to cocaine and 3,4-methylenedioxymethanphetamine (MDMA, ecstasy), given alone or in combination with alcohol, on memory performance, adult hippocampal neurogenesis and neurotoxicity. Rats were trained two weeks after the drug treatments in the radial arm maze. The results showed that only rats exposed to combinations of alcohol and MDMA exhibited significant memory deficits. Alcohol, MDMA and combinations thereof significantly decreased 5-bromodeoxyuridine labeling in the dentate gyrus (DG), indicating reduced survival of neuronal precursors. None of the treatments altered the length of the dendritic arbors of doublecortin (DCX)-positive neurons or the number and length of DCX-negative gaps in the DG. Thus, changes in adult neurogenesis were not causally related to the cognitive alterations induced by the treatments. Only the combination of alcohol and MDMA significantly decreased the population of mature granule neurons in the DG and increased the presence of cluster of differentiation 11b+ reactive microglia in the bordering areas of the subgranular zone. Critically, memory impairment was correlated with granule cell depletion. These observations demonstrate that exposure to alcohol and MDMA during adolescence, at doses that do not provoke apparent cognitive impairment when given separately, causes neurotoxic alterations affecting the DG region as well as persistent memory deficits. The findings highlight the elevated risk associated with the concurrent recreational use of alcohol and MDMA.
最近对药物消费的趋势评估显示，青少年和年轻人在狂欢、俱乐部和大学校园里同时使用多种药物的情况有所增加。我们在青春期大鼠中研究了可卡因和 3,4-亚甲二氧基甲基苯丙胺（摇头丸，迷幻药）单独或与酒精联合重复暴露对记忆表现、成年海马神经发生和神经毒性的影响。在药物处理后两周，大鼠在放射臂迷宫中接受训练。结果表明，只有暴露于酒精和 MDMA 组合的大鼠表现出明显的记忆缺陷。酒精、MDMA 及其组合显著降低了齿状回（DG）中的 5-溴脱氧尿苷标记，表明神经元前体的存活减少。这些处理都没有改变双皮质素（DCX）阳性神经元的树突分支长度或 DG 中 DCX 阴性间隙的数量和长度。因此，成年神经发生的变化与治疗引起的认知改变没有因果关系。只有酒精和 MDMA 的组合显著降低了 DG 中成熟颗粒神经元的数量，并增加了颗粒下区边缘区分化簇 11b+反应性小胶质细胞的存在。重要的是，记忆障碍与颗粒细胞耗竭有关。这些观察结果表明，在青春期暴露于酒精和 MDMA 会导致神经毒性改变，影响 DG 区域，并持续出现记忆缺陷，而这些剂量单独使用时不会引起明显的认知障碍。这些发现强调了同时滥用酒精和 MDMA 所带来的高风险。
