Neural Mechanisms of Risk Preference Following Adolescent Alcohol Exposure

描述（由申请人提供）：在青春期，个人经常接受他们的第一次接触酒精，并在大量摄入或暴饮暴食的事件中这样做的比例很大。这种经历可能是问题饮酒的前提，并与决策障碍有关。最近，它已被证明，青少年饮酒足以产生长期的干扰啮齿动物的风险为基础的决策。青春期是大脑发育成熟的关键时期，酒精的使用可能会破坏大脑发育。具体来说，中脑边缘多巴胺系统已被证明是有害的改变慢性酒精暴露在青春期。多巴胺的阶段性增加是由奖励结果和相关线索引起的。这些信号已经被证明与奖励的大小和概率成比例，与奖励成本一起，构成了最佳决策的基本组成部分。重要的是，所有这些属性的决策机构被认为是利用滥用的物质。事实上，在有青少年酒精暴露史的动物中，有风险但不安全的选择的阶段性多巴胺信号增加。这些发现表明，阶段性多巴胺释放的变化，作为酒精暴露的结果，可能是选择行为偏差的基础，并促进风险偏好。因此，据推测，青少年酒精暴露影响风险偏好，通过调制多巴胺系统，这种调制扰动一个或多个三个基本要素的决策：成本编码，风险评估，和/或编码的奖励结果在学习过程中。本提案将以三个具体目标检验这些假设。目标1将检验风险偏好是从成本不敏感性演变而来的假设，在这种情况下，预期的回报价值不会根据与采购相关的成本增加而贴现。目标2将检验风险偏好源于风险评估减少的假设，以及不确定性可能自相矛盾地提高价值（即“赌博嗡嗡声”）的命题。目标3将检验风险偏好是强化学习过程中奖励结果编码异常的结果这一假设。

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.