Impulsive choice and impulsive action predict vulnerability to distinct stages of nicotine seeking in rats
Impulsive choice and impulsive action predict vulnerability to distinct stages of nicotine seeking in rats
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DOI：
10.1016/j.biopsych.2007.07.011
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发表时间：
2008-02-01
影响因子：
10.6
通讯作者：
De Vries, Taco J.
中科院分区：
文献类型：
--
作者：
Diergaarde, Leontien;Pattij, Tommy;De Vries, Taco J.
背景：虽然大量吸烟与人类的冲动有关，但尚不清楚不良的冲动控制是否代表尼古丁依赖病因学中的危险因素。方法：为了解决这个问题，根据延迟奖励任务（冲动选择）和5选择串行反应时间任务（冲动行动）中冲动的个体差异来选择大鼠。随后，对大鼠进行尼古丁自我给药（SA）范例，以测量尼古丁和尼古丁相关刺激的动机特性。在不同的组中，确定了从几个中边缘脑区域获得的切片制剂中电诱发的多巴胺释放的差异。结果：冲动行为与启动和维持尼古丁SA的动机增强相关。相比之下，冲动选择预示着戒烟期间抑制尼古丁寻求的能力减弱，并且在重新暴露于尼古丁线索时更容易复发。冲动行为与伏隔核多巴胺释放减少相关，冲动选择与伏隔核、壳层和内侧前额皮质多巴胺释放减少相关。结论：冲动的子维度与尼古丁 SA 之间的强相关性意味着旨在改善冲动控制的干预措施可能有助于降低对尼古丁依赖的易感性和/或导致成功戒烟。
Background: Although heavy smoking has been associated with impulsivity in humans, it is not clear whether poor impulse control represents a risk factor in the etiology of nicotine dependence.Methods: To address this issue, rats Were selected on the basis of individual differences in impulsivity in the delayed reward task (impulsive choice) and the 5-choice serial reaction time task (impulsive action). Subsequently, rats were subjected to a nicotine self-administration (SA) paradigm tailored to measure the motivational properties of nicotine and nicotine-associated stimuli. In separate groups, differences in electrically evoked dopamine release in slice preparations obtained from several mesolimbic brain regions were determined.Results: Impulsive action was associated with an enhanced motivation to initiate and maintain nicotine SA. In contrast, impulsive choice predicted a diminished ability to inhibit nicotine seeking during abstinence and an enhanced vulnerability to relapse upon re-exposure to nicotine cues. Impulsive action was associated with reduced dopamine release in the accumbens core and impulsive choice with reduced dopamine release in accumbens core, shell, and medial prefrontal cortex.Conclusions: The strong association between sub-dimensions of impulsivity and nicotine SA implies that interventions aimed to improve impulse control might help to reduce susceptibility to nicotine dependence and/or lead to successful smoking cessation.