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

:以前的研究表明,阻断儿茶酚胺神经递质再摄取的药物可改善诸如注意缺陷多动障碍(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,并且与自杀风险增加有关。本研究使用5-choice系列反应时间任务(一种在啮齿动物中引起注意和冲动的模型)对一种或多种单胺再摄取转运蛋白具有亲和力的药物进行了研究。我们还测试了α(2)-肾上腺素受体拮抗剂,咪唑烷和新型抗抑郁药阿戈美拉汀的作用,它们均通过非重摄取机制增加了皮质去甲肾上腺素的浓度。使用文拉法辛,5-羟色胺和去甲肾上腺素再摄取抑制剂(SNRI)观察到冲动控制有所改善,但安非他酮(多巴胺和去甲肾上腺素再摄取抑制剂)观察不到。西布曲明(SNRI)在测试的最高剂量下可将早反应降低〜50%,但这并不明显。测试的所有三个SSRI均以剂量依赖的方式降低了过早的反应,尽管也减慢了反应和收集潜伏期。依达唑烷和阿戈美拉汀均未显着降低过早反应,表明在所测试的剂量下缺乏疗效。在最高测试剂量下,西布曲明(SNRI),氟西汀(SSRI)和帕罗西汀(SSRI)均未增加所测试药物的注意力。这些数据表明,在该模型中,SNRI和SSRI降低了过早反应,但特异性低于去甲肾上腺素特异性再摄取抑制剂。在该模型中,SSRI并未在冲动控制中引起任何特定的损害。

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