Laboratory of Neuropsychiatry, Mental Health Services Copenhagen, Denmark.
Behav Brain Res. 2012 Mar 1;228(1):169-75. doi: 10.1016/j.bbr.2011.12.006. Epub 2011 Dec 9.
Selective serotonin re-uptake inhibitors are increasingly used for the treatment of adolescents with behavioural disorders. However, the effect of this class of drugs during this sensitive period of brain development has not been extensively investigated. In this study we examine the effect of subchronic treatment with the selective serotonin re-uptake inhibitor, fluoxetine (10 mg/kg/day, i.p.) throughout adolescence (postnatal day 28-60) on learning and memory in the rat. Learning and memory were assessed at two time points: during adolescence, while the animals were being treated with fluoxetine and in young adulthood, 40 days after the termination of fluoxetine treatment. Fluoxetine treated rats were compared to a saline injected control group with respect to spatial navigation in the water maze, object recognition and object-in-place recognition memory. Additionally open field behaviour was examined. In adolescent rats fluoxetine treatment impaired water-maze probe trial performance and object recognition at intertrial intervals of 15 and 60 min, while leaving object-in-place recognition memory unaffected. In the open field the fluoxetine treated animals displayed reduced exploratory activity and higher levels of anxiety. Training the animals to a new platform position in young adulthood showed that the rats that had been treated with fluoxetine during adolescence were significantly slower to acquire this new spatial information. Adolescent fluoxetine treatment had no effect on cell proliferation in dorsal dentate gyrus and subgranular zone in young adulthood. This calls for further studies examining the long-term effects of this class of antidepressants on adolescent brain development and behaviour.
选择性 5-羟色胺再摄取抑制剂（SSRIs）越来越多地被用于治疗行为障碍的青少年。然而，在大脑发育的这个敏感时期，这类药物的效果并没有被广泛研究。在这项研究中，我们研究了亚慢性治疗对选择性 5-羟色胺再摄取抑制剂氟西汀（10mg/kg/天，腹腔注射）在青春期（出生后第 28-60 天）对大鼠学习和记忆的影响。学习和记忆在两个时间点进行评估：青春期时，动物正在接受氟西汀治疗，以及在青年期，即氟西汀治疗结束后 40 天。将氟西汀治疗的大鼠与生理盐水注射的对照组进行比较，以评估它们在水迷宫中的空间导航、物体识别和物体位置识别记忆。此外，还检查了开阔场行为。在青春期大鼠中，氟西汀治疗会损害水迷宫探测试验表现和 15 和 60 分钟时的物体识别，但不会影响物体位置识别记忆。在开阔场中，氟西汀治疗的动物表现出较低的探索活动和更高的焦虑水平。在青年期训练动物到新的平台位置时，发现在青春期接受氟西汀治疗的大鼠明显较慢地获得新的空间信息。在青年期，氟西汀治疗对成年后脑背齿状回和颗粒下区的细胞增殖没有影响。这需要进一步研究，以检查这类抗抑郁药对青少年大脑发育和行为的长期影响。
