Dopaminergic modulation of risky decision-making.
Dopaminergic modulation of risky decision-making.
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DOI：
10.1523/jneurosci.3772-11.2011
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发表时间：
2011-11-30
期刊：
影响因子：
--
通讯作者：
Setlow B
中科院分区：
文献类型：
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作者：
Simon NW;Montgomery KS;Beas BS;Mitchell MR;LaSarge CL;Mendez IA;Bañuelos C;Vokes CM;Taylor AB;Haberman RP;Bizon JL;Setlow B
许多精神疾病的特征是异常的风险决策和多巴胺受体表达失调。目前的研究旨在确定不同的多巴胺受体亚型如何调节年轻成年大鼠的冒险行为，使用“风险决策任务”，包括在小“安全”奖励和伴随不良后果的大“风险”奖励之间进行选择。老鼠在任务中的风险偏好表现出相当大、稳定的个体差异，这与奖励动机、焦虑或疼痛敏感性的多种衡量指标无关。 D2 样受体的全身激活大大减弱了冒险行为，而作用于 D1 样受体的药物则没有效果。全身使用安非他明还可以减少冒险行为，这种作用可以通过 D2 样（但不是 D1 样）受体阻断来减弱。多巴胺受体 mRNA 表达在一组单独的未接受过药物治疗的大鼠中进行了评估，这些大鼠的特征是该任务。伏隔核壳和岛叶皮质中的 D1 mRNA 表达与冒险行为呈正相关，而眶额和内侧前额叶皮质中的 D2 mRNA 表达则预测相反非线性模式中的风险偏好。此外，背侧纹状体中较低水平的 D2 mRNA 与较高的冒险行为相关。这些数据强烈暗示前额叶皮层纹状体回路中的多巴胺信号在调节决策过程中涉及奖励信息与不良后果风险的整合。
Many psychiatric disorders are characterized by abnormal risky decision-making and dysregulated dopamine receptor expression. The current study was designed to determine how different dopamine receptor subtypes modulate risk-taking in young adult rats, using a “Risky Decision-making Task” that involves choices between small “safe” rewards and large “risky” rewards accompanied by adverse consequences. Rats showed considerable, stable individual differences in risk preference in the task, which were not related to multiple measures of reward motivation, anxiety, or pain sensitivity. Systemic activation of D2-like receptors robustly attenuated risk-taking, whereas drugs acting on D1-like receptors had no effect. Systemic amphetamine also reduced risk-taking, an effect which was attenuated by D2-like (but not D1-like) receptor blockade. Dopamine receptor mRNA expression was evaluated in a separate cohort of drug-naive rats characterized in the task. D1 mRNA expression in both nucleus accumbens shell and insular cortex was positively associated with risk-taking, while D2 mRNA expression in orbitofrontal and medial prefrontal cortex predicted risk preference in opposing nonlinear patterns. Additionally, lower levels of D2 mRNA in dorsal striatum were associated with greater risk-taking. These data strongly implicate dopamine signaling in prefrontal corticalstriatal circuitry in modulating decision-making processes involving integration of reward information with risks of adverse consequences.