Departments of Psychology, Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, WA 98195, USA.
Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5466-71. doi: 10.1073/pnas.1017732108. Epub 2011 Mar 14.
Several emerging theories of addiction have described how abused substances exploit vulnerabilities in decision-making processes. These vulnerabilities have been proposed to result from pharmacologically corrupted neural mechanisms of normal brain valuation systems. High alcohol intake in rats during adolescence has been shown to increase risk preference, leading to suboptimal performance on a decision-making task when tested in adulthood. Understanding how alcohol use corrupts decision making in this way has significant clinical implications. However, the underlying mechanism by which alcohol use increases risk preference remains unclear. To address this central issue, we assessed dopamine neurotransmission with fast-scan cyclic voltammetry during reward valuation and risk-based decision making in rats with and without a history of adolescent alcohol intake. We specifically targeted the mesolimbic dopamine system, the site of action for virtually all abused substances. This system, which continuously develops during the adolescent period, is central to both reward processing and risk-based decision making. We report that a history of adolescent alcohol use alters dopamine signaling to risk but not to reward. Thus, a corruption of cost encoding suggests that adolescent alcohol use leads to long-term changes in decision making by altering the valuation of risk.
几种新兴的成瘾理论描述了滥用物质如何利用决策过程中的脆弱性。这些脆弱性被认为是由于正常大脑估值系统的药理学上受损的神经机制引起的。研究表明，青春期大鼠大量饮酒会增加风险偏好，导致成年后在决策任务上表现不佳。了解酒精是如何以这种方式破坏决策的，具有重要的临床意义。然而，酒精使用增加风险偏好的潜在机制仍不清楚。为了解决这个核心问题，我们使用快速扫描循环伏安法评估了有和没有青春期酒精摄入史的大鼠在奖励估值和基于风险的决策过程中的多巴胺神经传递。我们特别针对中脑边缘多巴胺系统，该系统是几乎所有滥用物质的作用部位。这个系统在青春期不断发育，是奖励处理和基于风险的决策的核心。我们报告说，青春期酒精使用史会改变多巴胺对风险的信号传递，但不会改变对奖励的信号传递。因此，成本编码的腐败表明，青少年饮酒会通过改变风险的估值，导致决策的长期变化。
