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首页> 外文期刊>Alcohol >Repeated ethanol treatment in adolescent rats alters cortical NMDA receptor.
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Repeated ethanol treatment in adolescent rats alters cortical NMDA receptor.

机译:在青春期大鼠中反复进行乙醇治疗会改变皮质NMDA受体。

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Earlier we have reported that repeated ethanol treatment during adolescence causes long-lasting impairments in spatial learning and memory. The present study was undertaken to determine the cellular mechanisms underlying the persistent ethanol-induced cognitive dysfunction in adolescent male rats. Since in adult animals ethanol is known to affect the N-methyl-d-aspartate (NMDA) receptor-gated ion channel, the hypothesis tested here was that adolescent ethanol exposure modulates NMDA receptor (NR) regulation in the brain. Adolescent male rats were injected daily with ethanol (2g/kg intraperitoneally) for 5 consecutive days. Control rats received isovolumetric saline for the same number of days. Groups of control and experimental rats were sacrificed 7 days after the last ethanol/saline administration, and NR activity was measured in specific brain regions (frontal cortex, hippocampus) using the [(3)H]MK-801 binding assay. In addition, some rats were sacrificed and their brains were used to investigate changes in NR pharmacology by measuring specific NR2 subunits immunohistochemically. Compared to saline-treated controls, ethanol-treated rats showed significant increases in [(3)H]MK-801 maximal binding in the frontal cortex. This was associated with increased cortical NR2B subunit protein. [(3)H]MK-801 binding in the hippocampus was minimally affected. These results indicate that ethanol exposure during the adolescent period produces brain region-specific alterations in NR activity. These changes are different from those reported in literature for ethanol administration during the perinatal period or adulthood. Together, these data suggest that adolescence represents a unique stage in brain development in its long-term sensitivity to ethanol.
机译:先前我们曾报道过,青春期反复进行乙醇治疗会导致空间学习和记忆力的长期损害。进行本研究以确定青春期雄性大鼠中持续乙醇诱导的认知功能障碍的细胞机制。由于已知在成年动物中乙醇会影响N-甲基-d-天冬氨酸(NMDA)受体门控的离子通道,因此此处测试的假设是青少年乙醇暴露会调节大脑中NMDA受体(NR)的调节。每天向成年雄性大鼠连续5天注射乙醇(2g / kg腹膜内)。对照大鼠在相同天数内接受等容盐水。在最后一次乙醇/盐水给药后7天,将对照组和实验组大鼠处死,并使用[(3)H] MK-801结合测定法测量特定大脑区域(额叶皮层,海马区)的NR活性。此外,处死了一些大鼠,并通过免疫组织化学方法测量了特定的NR2亚基,将它们的大脑用于研究NR药理学的变化。与盐水处理的对照组相比,乙醇处理的大鼠在额叶皮质中显示[(3)H] MK-801最大结合的显着增加。这与增加的皮质NR2B亚基蛋白有关。 [(3)H] MK-801在海马中的结合受到最小的影响。这些结果表明,青少年时期的乙醇暴露会导致NR活性在大脑区域发生特定变化。这些变化与文献报道的围产期或成年期使用乙醇的变化不同。总之,这些数据表明,青春期对乙醇的长期敏感性代表了大脑发育的独特阶段。

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