Project 3: Neural Encoding of the Incentive Value Attributed to Food and Drug Cue

项目总结（见说明）： 与食物和药物奖励相关的线索获得1）预测特性，以及唤起条件反应的能力，以及2）激励特性，从而吸引，加强和激励行为的能力。这些后一种特性可能在强迫性行为障碍（包括成瘾）的发展中尤为重要。然而，预测线索并不一定具有作为激励刺激的能力。事实上，在线索的影响能力方面， 行为例如，虽然有些人能够在一生中随意使用毒品，但其他人会上瘾，难以保持禁欲，特别是在与吸毒有关的人，地点和其他线索存在的情况下。通过检查对食物线索的行为反应，我们已经确定了将激励价值归因于这些线索（“信号追踪者”）的大鼠，并且对这些线索更敏感。 药物线索对吸毒行为和复吸的影响。相反，“目标追踪者”不把激励价值归因于食物线索，也不受药物线索的影响。对大脑活动中线索诱发变化的研究发现，基底神经节的腹侧区域（包括延髓核[NAcc]和腹侧苍白球[VP]）处理与食物和药物线索相关的信息。然而，直到最近， 很难描述哪些方面（即，预测性或激励性）的线索进行加工，以及滥用药物是否改变了激励价值的加工。本提案中描述的实验将利用符号和目标跟踪器的个体差异来确定NAcc和VP过程中是否存在符号和目标跟踪器中食物线索的激励与预测特性，以及在多大程度上 神经化学物质多巴胺参与其中。为此，我们将使用体内单单位记录来测量巴甫洛夫和药物自我给药实验中对线索的神经反应。我们的总体假设是，VP和NAcc神经元将更响应于奖励线索的预测属性时，在这些实验中的激励属性。

PROJECT SUMMARY (See instructions): Cues associated with food and drug rewards acquire 1) predictive properties, and the ability to evoke conditioned responses, and 2) incentive properties, and thus the ability to attract, reinforce, and motivate behavior. These latter properties may be especially important in the development of compulsive behavioral disorders, including addiction. However, predictive cues do not necessarily have the ability to act as incentive stimuli. In fact, there are substantial individual differences in the ability of cues to influence behavior. For example, while some people are able to use drugs casually throughout their lifetime, others become addicted, having difficulty remaining abstinent, especially in the presence of people, places, and other cues associated with drug-taking. By examining the behavioral responses to food cues, we have identified rats that attribute incentive value to these cues ("sign-trackers"), and are more sensitive to the effects of drug cues on drug-taking behavior and relapse. In contrast, "goal-trackers" do not attribute incentive value to food cues and are unaffected by drug cues. Studies of cue-evoked changes in brain activity have found that ventral regions of the basal ganglia (including the nucleus accumbens [NAcc] and ventral pallidum [VP]) process information related to both food and drug cues. However, until recently, it has been difficult to delineate what aspects (i.e., predictive or incentive) of these cues are processed, and whether the processsing of incentive value is altered by abused drugs. The experiments described within this proposal will utilize individual differences of sign- and goal-trackers to determine whether the NAcc and VP process incentive vs. predictive properties of food cues in sign- and goal-trackers, and to what extent the neurochemical dopamine is involved. To this end, we will measure the neural response to cues in Pavlovian and drug self-administration experiments using in-vivo single-unit recordings. Our overall hypothesis is that VP and NAcc neurons will be more responsive to the incentive properties than to the predictive properties of reward cues when presented within these experiments.