Previous studies have shown that drugs which block the reuptake of catecholamine neurotransmitters improve impulse control in diseases such as attention deficit hyperactivity disorder (ADHD). Serotonin-specific reuptake inhibitors (SSRI) lack efficacy in ADHD and have been linked to increased suicide risk. The present study investigated drugs with affinity for one or more of the monoamine reuptake transporters using the 5-choice serial reaction time task, a model of attention and impulsivity in rodents. We also tested the effects of the alpha(2)-adreoceptor antagonist, idazoxan and novel antidepressant, agomelatine, which both increase cortical noradrenaline concentrations through non-reuptake mechanisms. Improvements in impulse control were observed with venlafaxine, a serotonin and noradrenaline re-uptake inhibitor (SNRI) but not bupropion (dopamine and noradrenaline re-uptake inhibitor). Sibutramine (SNRI) reduced premature responses by ~50% at the highest dose tested but this was not significant. All three of the SSRIs tested reduced premature responding in a dose-dependent manner, although also slowed response and collection latencies. Neither idazoxan nor agomelatine significantly reduced premature responding, suggesting a lack of efficacy at the doses tested. None of the drugs tested improved attention in this task but sibutramine (SNRI), fluoxetine (SSRI) and paroxetine (SSRI) all increased omissions at the highest dose tested. These data suggest that the SNRIs and SSRIs reduce premature responding but tend to be less specific than noradrenaline specific reuptake inhibitors in this model. SSRIs did not induce any specific impairment in impulse control in this model.

译文

先前的研究表明,阻断儿茶酚胺神经递质再摄取的药物可改善注意力缺陷多动障碍 (ADHD) 等疾病的冲动控制。血清素特异性再摄取抑制剂 (SSRI) 在ADHD中缺乏疗效,并与自杀风险增加有关。本研究使用5选择系列反应时间任务 (啮齿动物的注意力和冲动性模型) 研究了对一种或多种单胺再摄取转运蛋白具有亲和力的药物。我们还测试了 α (2)-受体拮抗剂咪唑嗪和新型抗抑郁药阿戈米拉汀的作用,它们均通过非再摄取机制增加皮质去甲肾上腺素浓度。使用文拉法辛 (一种5-羟色胺和去甲肾上腺素再摄取抑制剂 (SNRI)) 但未使用安非他酮 (多巴胺和去甲肾上腺素再摄取抑制剂) 观察到冲动控制的改善。在测试的最高剂量下,西布曲明 (SNRI) 将过早反应降低约50%,但这并不显著。测试的所有三个ssri均以剂量依赖性方式减少了过早反应,尽管也减慢了反应和收集延迟。依达唑烷和阿戈米拉汀均未显着降低过早反应,表明在测试剂量下缺乏疗效。测试的药物均未提高此任务中的注意力,但西布曲明 (SNRI),氟西汀 (SSRI) 和帕罗西汀 (SSRI) 在测试的最高剂量下均增加了遗漏。这些数据表明,在该模型中,snri和SSRIs减少了过早反应,但特异性不如去甲肾上腺素特异性再摄取抑制剂。在该模型中,SSRIs不会在冲动控制中引起任何特定的损害。

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