Risk-preferring rats make worse decisions and show increased incubation of craving after cocaine self-administration
Risk-preferring rats make worse decisions and show increased incubation of craving after cocaine self-administration
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DOI：
10.1111/adb.12388
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发表时间：
2017-07-01
影响因子：
3.4
通讯作者：
Winstanley, Catharine A.
中科院分区：
文献类型：
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作者：
Ferland, Jacqueline-Marie N.;Winstanley, Catharine A.
不适应的决策可能在成瘾的发展和维持中起着不可或缺的作用。物质依赖的个体在爱荷华赌博任务中做出更冒险的选择，这些缺陷在戒断期间持续存在，并预示着复发。然而，临床研究尚不清楚这种认知障碍是药物使用的原因还是后果。我们对雄性Long-Evans大鼠进行了大鼠赌博任务（一种啮齿类动物模拟的爱荷华赌博任务）的训练，以确定选择偏好如何影响可卡因自我给药、戒断和渴望潜伏期，并受其影响。在基线时表现出对危险、不利选择的偏好的大鼠是唯一受到可卡因自我给药不利影响的。当在同一时间段内评估决策时，这些大鼠的风险选择加剧，而最优决策者的选择模式不受影响。这种决策缺陷在戒断期间持续了30天，并与更大的线索诱导的渴望潜伏期相关。偏好冒险的大鼠在自我给药期间也有更多的寻求药物的反应。这些数据表明，在接触成瘾性药物之前的不良决策与倾向成瘾的行为表型有关，其特征是在可卡因自我给药和戒断期间进一步增加风险选择和增强对药物的反应。这些发现表明，在物质依赖人群中观察到的高风险决策不仅仅是间接的，而且对成瘾的脆弱性和严重程度做出了重要贡献，现在可以在实验室大鼠中有效地建模。
Maladaptive decision-making may play an integral role in the development and maintenance of an addiction. Substance-dependent individuals make riskier choices on the Iowa Gambling Task, and these deficits persist during withdrawal and are predictive of relapse. However, it is unclear from clinical studies whether this cognitive impairment is a cause or consequence of drug use. We trained male Long-Evans rats on the rat Gambling Task, a rodent analogue of the Iowa Gambling Task, to determine how choice preference influenced, and was influenced by, cocaine self-administration, withdrawal and incubation of craving. Rats that exhibited a preference for the risky, disadvantageous options at baseline were uniquely and adversely affected by cocaine self-administration. Risky choice was exacerbated in these rats when decision-making was assessed during the same diurnal period as cocaine self-administration, whereas the choice pattern of optimal decision-makers was unaffected. This decision-making deficit was maintained during 30 days of withdrawal and correlated with greater cue-induced incubation of craving. Risk-preferring rats also made more drug-seeking responses during cocaine self-administration. These data demonstrate that poor decision-making prior to contact with addictive drugs is associated with a pro-addictive behavioural phenotype, characterized by further increased risky choice and heightened responding for drug both during cocaine self-administration and withdrawal. Such findings indicate that the elevated risky decision-making observed in substance-dependent populations is not merely circumstantial, but makes an important contribution to addiction vulnerability and severity that can now be effectively modelled in laboratory rats.