Neural Mechanisms of Risk Preference Following Adolescent Alcohol Exposure

青少年酒精暴露后风险偏好的神经机制

基本信息

批准号：
9298370
负责人：
Paul E. M. Phillips
金额：
$ 30.9万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9298370
关键词：
Adolescence Adult Age Alcohol abuse Alcohol consumption Alcohols Animals Brain Choice Behavior Chronic Corpus striatum structure Cost Analysis Cues Decision Making Development Dopamine Drug abuse Elements Expectancy Exposure to Failure Feedback Gambling Generations Goals Impairment Individual Intake Learning Measures Modeling Neuromodulator Outcome Periodicity Pharmaceutical Preparations Phase Predictive Value Probability Process Psychological reinforcement Public Health Rattus Recording of previous events Reinforcement Schedule Rewards Risk Risk Assessment Rodent Scanning Signal Transduction Testing Time Uncertainty Work addiction adolescent alcohol exposure alcohol consequences alcohol exposure base binge drinking classical conditioning cost critical period discount discounting dopamine system dopaminergic neuron expectation experience mesolimbic system neuromechanism preference reinforcer relating to nervous system reward processing transmission process underage drinking

项目摘要

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.

描述（由申请人提供）：在青春期，个人经常收到第一次接触酒精，并且在高摄入量或暴饮暴食期间很大一部分会这样做。这种经验可能是饮酒问题的前提，并且与决策障碍有关。最近，已经证明青少年饮酒足以产生啮齿动物中基于风险的决策的长期扰动。青春期是至关重要的成熟时期，饮酒可能会破坏大脑发育。具体而言，在青春期，慢性酒精暴露会证明中唇多巴胺系统被证明会持久改变。通过奖励结果和相关的提示，多巴胺的阶段性增加被引起。这些信号已被证明可以按照奖励的规模和概率进行扩展，并构成了最佳决策的基本组成部分。重要的是，认为决策机构的所有属性都被滥用的物质所剥削。实际上，具有青春期酒精暴露史的动物的质量多巴胺信号传达对风险，但不是安全的，但选择量增加。这些发现表明，由于酒精暴露，阶段性多巴胺释放的变化可能是选择行为的偏见并促进风险偏好的基础。因此，假设青少年酒精暴露会通过调节多巴胺系统影响风险偏好，并且这种调节使决策的三个基本要素中的一个或多个剥夺了一个或多个；成本编码，风险评估和/或学习过程中的奖励结果编码。当前的提案将以三个特定目标检验这些假设。 AIM 1将检验以下假设：在预期的奖励价值基于与其采购相关的成本增加的情况下，风险偏好从成本不敏感性演变而来。 AIM 2将检验以下假设：风险偏好是由于风险评估减少以及不确定性可能会矛盾地提高价值的主张而引起的（即“赌博嗡嗡声”）。 AIM 3将检验以下假设：风险偏好是对强化学习过程中奖励结果异常编码的结果。