Cognitive impairments from developmental exposure to serotonergic drugs: citalopram and MDMA.
Cognitive impairments from developmental exposure to serotonergic drugs: citalopram and MDMA.
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DOI：
10.1017/s1461145712001447
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发表时间：
2013-07
期刊：
影响因子：
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通讯作者：
Vorhees CV
中科院分区：
文献类型：
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作者：
Schaefer TL;Grace CE;Braun AA;Amos-Kroohs RM;Graham DL;Skelton MR;Williams MT;Vorhees CV
我们以前表明，发展中的3，4-亚甲二氧基甲基苯丙胺（MDMA）治疗诱导长期的空间和自我中心的学习和记忆缺陷和5-羟色胺（5-HT）的减少。在脑发育过程中，5-HT是一种神经营养因子，影响神经发生、突触发生、迁移和靶区组织。大鼠产后第11-20天（PD）（边缘系统发育时期，接近人类妊娠晚期大脑发育）给予MDMA（10 mg/kg×4/d，间隔2小时），可诱导治疗期间5-HT减少50%，评估为成年时减少20%。为了确定5-HT减少是否是认知缺陷的原因，我们在一项伴随研究中使用西酞普兰（Cit）预处理来抑制MDMA对5-HT再摄取的影响。Cit使MDMA诱导的5-HT减少减弱50%。在此，我们测试了Cit（5或7.5 mg/kg×2/d）预处理是否减弱MDMA的认知效应。在每窝中，在PD 11 -20用生理盐水（Sal）+MDMA、Cit+MDMA、Cit+Sal或Sal+Sal处理不同后代。Cit预处理既不能改善空间学习记忆，也不能改善自我中心学习记忆。出乎意料的是，Cit+Sal（两种剂量）产生的空间和自我中心学习缺陷与Sal+MDMA引起的缺陷一样严重。这是第一个数据显示认知缺陷造成的发展暴露于选择性血清素再摄取抑制剂。这些数据表明，需要进一步研究抗抑郁药在怀孕期间的长期安全性。
We previously showed that developmental 3,4-methylenedioxymethamphetamine (MDMA) treatment induces long-term spatial and egocentric learning and memory deficits and serotonin (5-HT) reductions. During brain development, 5-HT is a neurotrophic factor influencing neurogenesis, synaptogenesis, migration, and target field organization. MDMA (10 mg/kg×4/d at 2 h intervals) given on post-natal day (PD) 11–20 in rats (a period of limbic system development that approximates human third trimester brain development) induces 50% reductions in 5-HT during treatment and 20% reductions when assessed as adults. To determine whether the 5-HT reduction is responsible for the cognitive deficits, we used citalopram (Cit) pretreatment to inhibit the effects of MDMA on 5-HT reuptake in a companion study. Cit attenuated MDMA-induced 5-HT reductions by 50%. Here we tested whether Cit (5 or 7.5 mg/kg×2/d) pretreatment attenuates the cognitive effects of MDMA. Within each litter, different offspring were treated on PD11–20 with saline (Sal)+MDMA, Cit+MDMA, Cit+Sal or Sal+Sal. Neither spatial nor egocentric learning/memory was improved by Cit pretreatment. Unexpectedly, Cit+Sal (at both doses) produced spatial and egocentric learning deficits as severe as those caused by Sal+MDMA. These are the first data showing cognitive deficits resulting from developmental exposure to a selective serotonin reuptake inhibitor. These data indicate the need for further research on the long-term safety of antidepressants during pregnancy.