Impulsivity, Dopamine and the Behavioral Economics of Gambling

描述（由申请人提供）：延迟结果贬值的程度（延迟折扣）与人类药物滥用和病理性赌博相关。最近的证据表明，在实验动物中，高延迟折扣率可以预测药物服用，本提案将研究延迟折扣和赌博决定之间是否存在类似的关系。具体来说，我们将测试一个实证支持的延迟折扣定量模型的定量预测，该模型预测延迟折扣的程度应该可以预测对赌博结果的偏好——对延迟奖励折扣程度较高的个体应该比那些对延迟奖励折扣程度较低的个体更有可能赌博。实验1将通过首先量化三种大鼠品系的延迟折扣来验证这一预测，其中两种已知在5-羟色胺和多巴胺系统功能上存在差异。然后，我们将检验这些延迟折扣程度的应变差异是否预测了当这些选择导致经济损失时的后续赌博偏好。实验2将探讨丙哌索和PD 128 907（两种选择性D3激动剂）对Wistar大鼠延迟折扣程度和赌博偏好的作用。最近的临床证据表明，一些接受普拉克索治疗的帕金森患者经历了各种成瘾行为的病理水平，包括赌博。实验3将检验一种在鸽子和人类身上被证明有效的延迟容忍训练形式，是否能在一种特别冲动的大鼠品系（Lewis）中减少冲动选择，与一组接受虚假训练的Lewis大鼠相比。如果是这样，那么我们将确定延迟容忍训练组是否比假训练组选择更少的赌博。公共卫生相关性：与即时结果相比，人类和非人类都低估了延迟结果的价值。这种贴现过程与药物滥用和病态赌博有关。拟议的研究将检查可能影响延迟折扣和人类病理性赌博发展的生物学、药理学和治疗变量。

DESCRIPTION (provided by applicant): The degree to which delayed outcomes are devalued (delay discounting) is correlated with substance abuse and pathological gambling in humans. Recent evidence suggests that high rates of delay discounting are predictive of drug taking in laboratory animals and the present proposal will examine if a similar relation exists between delay discounting and the decision to gamble. Specifically, we will test the quantitative predictions of an empirically supported quantitative model of delay discounting which predicts that degree of delay discounting should be predictive of preference for gambling outcomes - individuals that discount delayed rewards to a greater degree should be more likely to gamble than those who discount these rewards to a lesser extent. Experiment 1 will test this prediction by first quantifying delay discounting in three rat strains, two of which are known to differ in 5-HT and dopamine system functioning. Then we will examine if these strain differences in degree of delay discounting are predictive of subsequent preferences for gambling when these choices result in economic losses. Experiment 2 will investigate the role of pramipexole and PD 128 907 (two selective D3 agonists) on Wistar rats' degree of delay discounting and preferences for gambling. Recent clinical evidence suggests that some Parkinson patients treated with pramipexole experience pathological levels of a variety of addictive behaviors, including gambling. Experiment 3 will examine if a form of delay tolerance training that has proven effective in pigeons and humans can decrease impulsive choices in a particularly impulsive rat strain (Lewis) when compared with a control group of Lewis rats given sham training. If so, then we will determine if the delay-tolerance-trained group chooses to gamble less than the sham-trained group. PUBLIC HEALTH RELEVANCE: Humans and nonhumans alike discount the value of delayed outcomes relative to immediate outcomes. This discounting process is correlated with substance abuse and pathological gambling. The proposed research will examine biological, pharmacological, and therapeutic variables that may affect delay discounting and the development of human pathological gambling.