Variation in Motivational Properties of Reward Cues: Implications for Addiction

描述（由申请人提供）：我们的许多日常行为是由与促进生存的奖励相关的刺激（线索）控制的-例如，它们吸引我们寻找食物来源和潜在的伴侣。然而，这种暗示也会促进适应不良的行为。食物的暗示会导致暴饮暴食，而与药物奖励相关的暗示则会促使药物使用并引发复发，从而导致成瘾。与奖励相关的线索（条件刺激，CS）只有当它们被归因于激励动机属性（“激励突出性”）时，才能有力地激励正常和适应不良行为，从而获得作为激励刺激的能力。在初步研究中，我们做了两个新的观察：（1） 奖励线索的条件刺激属性不足以使它们也起激励作用 刺激，和（2）有很大的变化，个别大鼠的倾向，属性奖励显着性的食物和药物线索，从而激励行为。这两个观察导致了一个从未被探索过的创新假设，即倾向于将激励显著性归因于药物线索的个体将特别难以抵制这些线索，因此特别容易上瘾。本计划项目的目的是检验这一假设，研究可能导致这种变异的神经生物学系统的运作，并确定这种表型与其他可能导致成瘾的“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，pror任何药物的经验，个人倾向于属性的激励显着性药物线索，以及这些人是否特别有可能发展成瘾样行为。项目2的重点是这种个体差异是否与使用快速扫描循环伏安法的丘脑核中多巴胺信号的变化有关，项目3使用电生理记录来确定这是否进一步反映在丘脑的主要输出，基底前脑/腹侧苍白球的神经编码中。最后，项目4将这些皮层下系统与皮层认知控制系统联系起来，并将探索皮层机制，这些机制可能会导致个体的认知脆弱性，这些个体倾向于将激励显着性归因于rewar线索。

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.