Neural Mechanisms of Risk Preference Following Adolescent Alcohol Exposure

描述(由申请人提供)：在青春期，个人通常第一次接触酒精，其中相当大一部分是在高摄入量或暴饮暴食的时期。这种经历可能是饮酒问题的先兆，并与决策障碍有关。最近，已经证明青少年饮酒足以对啮齿动物的基于风险的决策产生长期的扰动。青春期是大脑发育成熟的关键时期，饮酒可能会扰乱大脑发育。具体地说，中脑边缘多巴胺系统已被证明在青春期长期酒精暴露而发生持久改变。多巴胺的阶段性增加是由奖励的结果和相关的提示引起的。这些信号已被证明与回报的大小和概率成比例，这与回报成本一起构成了最优决策的基本组成部分。重要的是，决策机构的所有这些属性都被认为被滥用的物质所利用。事实上，在有青春期酒精暴露史的动物中，向有风险但不安全的选择发出信号的相性多巴胺增加了。这些发现表明，作为酒精暴露的结果，多巴胺的相态释放的变化可能是选择行为中的偏见的基础，并促进风险偏好。因此，假设青少年酒精暴露通过调节多巴胺系统来影响风险偏好，这种调节扰乱了决策的三个基本要素中的一个或多个：成本编码、风险评估和/或学习过程中奖励结果的编码。目前的提案将用三个具体目标来检验这些假设。目标1将检验这样一种假设，即风险偏好是从成本不敏感演变而来的，在这种情况下，预期奖励价值不会根据与其采购相关的不断增加的成本而打折。目标2将检验风险偏好是风险评估减少的结果的假设，以及不确定性可能矛盾地提高价值的命题(即“赌博嗡嗡声”)。目标3将检验风险偏好是强化学习过程中奖励结果异常编码的结果这一假设。

DESCRIPTION (provided by applicant): During adolescence, individuals often receive their first exposure to alcohol, and a significant proportion do so during episodes of high intake or bingeing. Such experience can be antecedent to problem drinking and is associated with impairments in decision making. Recently, it has been demonstrated that adolescent alcohol use is sufficient to produce long-term perturbation of risk-based decision making in rodents. Adolescence is a critical period of maturation where brain development may be disrupted by alcohol use. Specifically, the mesolimbic dopamine system has been shown to be enduringly altered by chronic alcohol exposure during adolescence. Phasic increases in dopamine are evoked by rewarding outcomes and associated cues. These signals have been shown to scale with the magnitude and probability of reward which, together with reward costs, make up the fundamental components of optimal decision making. Importantly, all of these attributes of the decision making apparatus are thought to be exploited by abused substances. Indeed, phasic dopamine signaling to risky, but not safe, options is increased in animals with a history of adolescent alcohol exposure. These findings suggest that changes in phasic dopamine release, as a consequence of alcohol exposure, could underlie biases in choice behavior and promote risk preference. Therefore, it is hypothesized that adolescent alcohol exposure influences risk preference through modulation of dopamine systems and that such modulation perturbs one or more of three fundamental elements of decision making; cost encoding, risk assessment, and/or the encoding of reward outcomes during learning. The current proposal will test these hypotheses with three specific aims. Aim 1 will test the hypothesis that risk preference evolves from cost insensitivity where anticipated reward value is not discounted based upon the increasing cost associated with its procurement. Aim 2 will test the hypothesis that risk preference results from diminished risk assessment and the proposition that uncertainty may paradoxically enhance value (i.e. a "gambling buzz"). Aim 3 will test the hypothesis that risk preference is a consequence of the aberrant encoding of reward outcomes during reinforcement learning.