Impulsive action and impulsive choice are mediated by distinct neuropharmacological substrates in rat
Impulsive action and impulsive choice are mediated by distinct neuropharmacological substrates in rat
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DOI：
10.1017/s1461145711001635
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发表时间：
2012-11-01
影响因子：
4.8
通讯作者：
Hanania, Taleen
中科院分区：
文献类型：
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作者：
Paterson, Neil E.;Wetzler, Caitlin;Hanania, Taleen
冲动性是一个异质结构，根据临床和临床前的行为措施，有一些初步的证据表明不同的神经生物学基板的冲动性的子组件。两个临床前试验，五选择系列反应时间任务（5-CSRTT）和延迟折扣任务（DDT），假设提供的措施，冲动的行动（过早反应）和冲动的选择（百分比选择延迟奖励），分别。在目前的研究中，我们发现去甲肾上腺素再摄取抑制剂托莫西汀减弱了5-CSRTT的过早反应，但对DDT无效。混合多巴胺/去甲肾上腺素再摄取抑制剂哌甲酯表现出相反的效果。此外，通过酮色林阻断5-HT 2A/C受体可降低过早反应，但对延迟奖励的选择百分比没有影响;通过SB 242084阻断5-HT 2C受体具有相反的效果。随访研究提供了5-HT 2A/C受体阻滞剂对托莫西汀对冲动行为影响的累加效应的一些有限证据。这些研究证明了在5-CSRTT和DDT测定中，刺激性与非刺激性注意缺陷多动障碍药物和5-HT亚型选择性配体的可分离特征。因此，本研究结果支持冲动的亚类，并表明5-HT受体亚型选择性拮抗剂可为以不同形式的冲动为特征的疾病提供治疗靶点。
Impulsivity is a heterogeneous construct according to clinical and preclinical behavioural measures and there is some preliminary evidence indicating distinct neurobiological substrates underlying the sub-components of impulsivity. Two preclinical assays, the five-choice serial reaction time task (5-CSRTT) and the delayed discounting task (DDT), are hypothesized to provide measures of impulsive action (premature responding) and impulsive choice (percent choice for delayed reward), respectively. In the present studies, we show that the norepinephrine reuptake inhibitor atomoxetine attenuated premature responding in the 5-CSRTT, but was ineffective in the DDT. The mixed dopamine/norepinephrine reuptake inhibitor methylphenidate exhibited an opposite profile of effects. In addition, blockade of 5-HT2A/C receptors via ketanserin decreased premature responding but had no effects on percent choice for delayed reward; blockade of 5-HT2C receptors via SB 242084 had opposite effects. Follow-up studies provided some limited evidence of additive effects of 5-HT2A/C receptor blockade on the effects of atomoxetine on impulsive action. These studies demonstrate dissociable profiles of stimulant vs. non-stimulant attention deficit hyperactivity disorder medications and 5-HT subtype-selective ligands, in the 5-CSRTT and DDT assays. Thus, the present findings support the sub-categorization of impulsivity and suggest that 5-HT receptor subtype-selective antagonists may provide therapeutic targets for disorders characterized by different forms of impulsivity.