Variation in Motivational Properties of Reward Cues: Implications for Addiction

描述(申请人提供)：我们的日常行为很大程度上受到与奖励相关的刺激(线索)的控制，这些奖励有助于生存--例如，它们将我们吸引到食物的来源和潜在的配偶那里。然而，这样的暗示也会促进不适应行为。食物暗示可能会引发暴饮暴食，而与药物奖励相关的暗示会刺激药物使用并引发复发，从而导致上瘾。与奖励相关的暗示(条件刺激)只有在被归因于激励性动机属性(“激励性显著”)的情况下，才能有力地激发正常行为和不适应行为，从而获得作为激励性刺激的能力。在初步研究中，我们做了两个新的观察：(1) 奖励提示的条件刺激特性不足以使它们也起到激励作用 (2)个体大鼠将激励突显归因于食物和药物线索的倾向存在很大差异，从而激励行为。这两个观察结果导致了一个从未被探索过的创新假设，即倾向于将激励突显归因于药物线索的人将特别难以抵抗这种线索，因此特别容易上瘾。该计划项目的目的是验证这一假设，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、证实任何吸毒经历，哪些人倾向于将激励突显归因于毒品线索，以及这些人是否特别有可能发展成瘾行为。项目2使用快速扫描循环伏安法，重点研究这种个体差异是否与伏隔核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伏隔核的主要输出--基底前脑/腹侧苍白球--的神经编码中。最后，项目4将这些皮质下系统与大脑皮层认知控制系统联系起来，并将探索大脑皮层机制，这些机制可能解释倾向于将激励突显归因于重战线索的个人的认知脆弱性。

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.