Variation in Motivational Properties of Reward Cues: Implications for Addiction

奖励线索动机特性的变化：对成瘾的影响

• 批准号: 8264821
• 负责人: Terry E. Robinson
• 金额: $ 136.57万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8264821
• 关键词: Accounting; Address; Animals; Behavior; Behavior Control; Behavioral; Cognitive; Consumption; Cues; Development; Dopamine; Drug usage; Food; Globus Pallidus; Goals; Hyperphagia; Impulse Control Disorders; Incentives; Individual; Individual Differences; Knowledge; Lead; Link; Motivation; Neurobiology; Nucleus Accumbens; Output; Partner in relationship; Pharmaceutical Preparations; Phenotype; Play; Pre-Clinical Model; Predictive Value; Process; Property; Public Health; Rattus; Recording of previous events; Relapse; Renaissance; Research; Rewards; Risk Factors; Role; Scanning; Series; Signal Transduction; Source; Stimulus; System; Testing; United States; Variant; Work; addiction; basal forebrain; base; classical conditioning; cognitive control; drug reward; drug seeking behavior; effective therapy; experience; innovation; motivated behavior; novel; operation; programs; psychologic; relating to nervous system; response; theories; trait

DESCRIPTION (provided by applicant): Much of our daily behavior is controlled by stimuli (cues) associated with rewards that promote survival - for example, they attract us to sources of food and to potential mates. However, such cues can also promote maladaptive behavior. Food cues can instigate overeating, and cues associated with drug rewards motivate drug use and instigate relapse, thus contributing to addiction. Cues associated with rewards (conditional stimuli, CSs) powerfully motivate both normal and maladaptive behavior only if they are attributed with incentive motivational properties ("incentive salience"), and thus acquire the ability to act as incentive stimuli. In preliminary studies we made two novel observations: (1) the conditional stimulus properties of reward cues are not sufficient for them to also act as incentive stimuli, and (2) there is large variation in the propensity of individual rats to attribute incentie salience to food and drug cues, and thus to motivate behavior. These two observations lead to an innovative hypothesis, never explored, which is that individuals prone to attribute Incentive salience to drug cues will have particular difficulty resisting such cues, and thus be especially vulnerable to addiction. The purpose of this Program Project is to test this hypothesis, to study the operation of neurobiological systems that may underlie this variation, and to determine the relationship between this phenotype and other "traits" that may confer vulnerability to addiction. Thus, Project 1 primarily involves behavioral studies to determine if it is possible to predict, pror to any drug experience, which individuals are prone to attribute incentive salience to drug cues and whether these individuals are especially likely to develop addiction-like behavior. Project 2 focuses on whether this individual variation is related to variation in dopamine signaling in the nucleus accumbens, using fast scan cyclic voltammetry, and Project 3 uses electrophysiological recordings to determine whether this is further reflected in neural encoding in the main output of the accumbens, the basal forebrain/ventral pallidum. Finally, Project 4 links these subcortical systems with cortical, cognitive control systems and will explore cortical mechanisms that may account for cognitive vulnerabilities in individuals prone to attribute incentive salience to rewar cues. PUBLIC HEALTH RELEVANCE: Addiction is a major public health problem in the United States. The goal of this Project is to use a preclinical model to delineate the psychological and neurobiological basis of individual differences in vulnerability to develop addiction-like behavior as this will help identify risk factors that will aid in the development of targeting interventionsand treatments.

描述（由申请人提供）：我们的许多日常行为都由与促进生存的奖励相关的刺激（提示）控制 - 例如，它们吸引我们进入食物来源和潜在的伴侣。但是，这种提示也可以促进适应不良的行为。食品提示可以激发暴饮暴食，与药物奖励相关的提示激励吸毒并激发复发，从而导致成瘾。与奖励（有条件刺激，CSS）相关的提示只有在将激励动机特性（“激励显着性”）归因时，才能有力地激励正常和适应不良的行为，从而获得充当激励刺激的能力。在初步研究中，我们进行了两个新颖的观察：（1） 奖励提示的条件刺激特性不足以使他们充当激励 刺激和（2）单个大鼠倾向将侵入性显着性归因于食品和药物提示，从而激励行为有很大的变化。这两种观察结果导致了创新的假设，从未探索过，这是个人容易将激励性显着性归因于毒品提示将有特别困难地抵抗这种提示，因此尤其容易受到成瘾的影响。该计划项目的目的是检验这一假设，研究可能是这种变化的神经生物学系统的运行，并确定可能赋予成瘾脆弱性的表型与其他“特征”之间的关系。因此，项目1主要涉及行为研究，以确定是否有可能预测任何药物体验，哪些人容易将激励显着性归因于药物线索以及这些人是否特别有可能发展类似成瘾的行为。项目2的重点是使用快速扫描环状伏安法与多巴胺信号传导的变化有关，使用快速扫描循环伏安法和项目3使用电生理记录来确定这是否进一步反映在伏anc的主要输出中的神经编码中。最后，项目4将这些皮层下系统与皮质的认知控制系统联系起来，并将探索可能解释个人的认知脆弱性的皮质机制，容易将激励性显着性归因于Rewar提示。 公共卫生相关性：成瘾是美国的主要公共卫生问题。该项目的目的是使用临床前模型来描述脆弱性的个体差异的心理和神经生物学基础，以发展成瘾行为，因为这将有助于确定有助于开发靶向干预措施和治疗的风险因素。