Dissociable effects of monoamine reuptake inhibitors on distinct forms of impulsive behavior in rats.
Dissociable effects of monoamine reuptake inhibitors on distinct forms of impulsive behavior in rats.
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DOI：
10.1007/s00213-011-2576-x
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发表时间：
2012-01
影响因子：
3.4
通讯作者：
Vanderschuren, Louk J. M. J.
中科院分区：
文献类型：
--
作者：
Baarendse, Petra J. J.;Vanderschuren, Louk J. M. J.
高度冲动是多动症、躁狂症、人格障碍和毒瘾等精神疾病的核心症状。针对多巴胺（DA）、去甲肾上腺素（NA）和/或5-羟色胺（5-HT）的药物在治疗冲动控制障碍中的有效性强调了单胺能神经传递在冲动性中的作用。然而，冲动行为在行为和神经上是异质的，在我们对单胺在冲动控制中的作用的理解中仍然存在一些警告。本研究旨在探讨DA、NA和5-HT在冲动性两个主要行为维度中的作用。评价了选择性DA（GBR 12909; 2.5-10 mg/kg）、NA（托莫西汀; 0.3-3.0 mg/kg）和5-HT（西酞普兰; 0.3-3.0 mg/kg）再摄取抑制剂以及苯丙胺（0.25-1.0 mg/kg）对五选择系列反应时间任务（5-CSRTT）中的冲动行为和延迟奖励任务（DRT）中的冲动选择的影响。在5-CSRTT中，在基线和长试验间隔（ITI）条件下进行神经药理学挑战，以增强任务中的冲动行为。苯丙胺和GBR 12909增加了5-CSRTT中的冲动行为和持续反应，降低了准确性和反应潜伏期。在5-CSRTT中，托莫西汀增加了基线条件下的遗漏错误和反应潜伏期。在长ITI下，托莫西汀还减少了过早和持续反应，并增加了准确性。西酞普兰改善了5-CSRTT的冲动控制。安非他明和GBR 12909，而不是西酞普兰或托莫西汀，减少了DRT中的冲动选择。DA神经传递的升高增加冲动行为，减少冲动选择。增加NA或5-HT神经传递减少冲动行为。
High levels of impulsivity are a core symptom of psychiatric disorders such as ADHD, mania, personality disorders and drug addiction. The effectiveness of drugs targeting dopamine (DA), noradrenaline (NA) and/or serotonin (5-HT) in the treatment of impulse control disorders emphasizes the role of monoaminergic neurotransmission in impulsivity. However, impulsive behavior is behaviorally and neurally heterogeneous, and several caveats remain in our understanding of the role of monoamines in impulse control. This study aims to investigate the role of DA, NA and 5-HT in two main behavioral dimensions of impulsivity. The effects of selective DA (GBR12909; 2.5–10 mg/kg), NA (atomoxetine; 0.3–3.0 mg/kg) and 5-HT (citalopram; 0.3–3.0 mg/kg) reuptake inhibitors as well as amphetamine (0.25–1.0 mg/kg) were evaluated on impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task (DRT). In the 5-CSRTT, neuropharmacological challenges were performed under baseline and long intertrial interval (ITI) conditions to enhance impulsive behavior in the task. Amphetamine and GBR12909 increased impulsive action and perseverative responding and decreased accuracy and response latency in the 5-CSRTT. Atomoxetine increased errors of omission and response latency under baseline conditions in the 5-CSRTT. Under a long ITI, atomoxetine also reduced premature and perseverative responding and increased accuracy. Citalopram improved impulse control in the 5-CSRTT. Amphetamine and GBR12909, but not citalopram or atomoxetine, reduced impulsive choice in the DRT. Elevation of DA neurotransmission increases impulsive action and reduces impulsive choice. Increasing NA or 5-HT neurotransmission reduces impulsive action.
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