Department of Psychology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.
J Neurosci. 2012 Oct 31;32(44):15450-7. doi: 10.1523/JNEUROSCI.0626-12.2012.
Individual differences in dopamine (DA) signaling, including low striatal D(2/3) receptors, may increase vulnerability to substance abuse, although whether this phenotype confers susceptibility to nonchemical addictions is unclear. The degree to which people use "irrational" cognitive heuristics when choosing under uncertainty can determine whether they find gambling addictive. Given that dopaminergic projections to the striatum signal reward expectancy and modulate decision-making, individual differences in DA signaling could influence the extent of such biases. To test this hypothesis, we used a novel task to model biased, risk-averse decision-making in rats. Animals chose between a "safe" lever, which guaranteed delivery of the wager, or an "uncertain" lever, which delivered either double the wager or nothing with 50:50 odds. The bet size varied from one to three sugar pellets. Although the amount at stake did not alter the options' utility, a subgroup of "wager-sensitive" rats increased their preference for the safe lever as the bet size increased, akin to risk aversion. In contrast, wager-insensitive rats slightly preferred the uncertain option consistently. Amphetamine increased choice of the uncertain option in wager-sensitive, but not in wager-insensitive rats, whereas a D(2/3) receptor antagonist decreased uncertain lever choice in wager-insensitive rats alone. Micro-PET and autoradiography using [(11)C]raclopride confirmed a strong correlation between high wager sensitivity and low striatal D(2/3) receptor density. These data suggest that the propensity for biased decision-making under uncertainty is influenced by striatal D(2/3) receptor expression, and provide novel support for the hypothesis that susceptibility to chemical and behavioral addictions may share a common neurobiological basis.
个体多巴胺（DA）信号传递的差异，包括纹状体 D2/3 受体水平较低，可能会增加对物质滥用的易感性，尽管这种表型是否会导致对非化学成瘾的易感性尚不清楚。人们在不确定的情况下选择时使用“不合理”认知启发式的程度可以决定他们是否会觉得赌博上瘾。鉴于多巴胺能投射到纹状体的信号传递奖励预期并调节决策，DA 信号传递的个体差异可能会影响这种偏见的程度。为了验证这一假设，我们使用一种新的任务在大鼠中模拟有偏差的、规避风险的决策。动物在“安全”杠杆和“不确定”杠杆之间进行选择，前者保证了赌注的兑现，后者则以 50:50 的概率获得双倍赌注或一无所有。赌注大小从一个到三个糖丸不等。尽管赌注的数量不会改变选项的效用，但一组“赌注敏感”的大鼠随着赌注大小的增加，会增加对安全杠杆的偏好，类似于风险规避。相比之下，“赌注不敏感”的大鼠则一直略微偏爱不确定的选择。安非他命增加了“赌注敏感”大鼠对不确定选择的选择，而不是“赌注不敏感”大鼠；而 D2/3 受体拮抗剂仅降低了“赌注不敏感”大鼠对不确定杠杆的选择。使用[(11)C]raclopride 的微 PET 和放射自显影证实，高赌注敏感性与纹状体 D2/3 受体密度之间存在很强的相关性。这些数据表明，在不确定情况下做出有偏差的决策的倾向受到纹状体 D2/3 受体表达的影响，并为化学和行为成瘾的易感性可能具有共同的神经生物学基础的假设提供了新的支持。
