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了1)预测性，以及唤起条件性反应的能力，2)激励属性，从而获得吸引、强化和激励行为的能力。后者在包括成瘾在内的强迫性行为障碍的发展过程中可能特别重要。然而，预测性线索并不一定具有激励刺激的能力。事实上，线索的影响能力有很大的个体差异 行为。例如，虽然有些人能够在一生中随意使用毒品，但另一些人却上瘾了，很难保持戒毒，特别是在人、地点和其他与吸毒有关的线索面前。通过检查对食物提示的行为反应，我们已经确定了将激励价值归因于这些提示的老鼠(“记号追踪器”)，并且对 吸毒线索对吸毒行为和复吸的影响。相比之下，“目标追踪者”不会将激励价值归因于食物线索，也不会受到药物线索的影响。对线索诱发的大脑活动变化的研究发现，基底神经节的腹侧区域(包括伏隔核[NAcc]和腹侧苍白球[Vp])处理与食物和药物线索有关的信息。然而，直到最近，它一直在 很难描述这些线索的哪些方面(即预测性或激励性)是被处理的，以及是否被滥用药物改变了激励性价值的处理。这项提案中描述的实验将利用手势和目标跟踪器的个体差异来确定NAcc和VP是否在手势和目标跟踪器中对食物线索的激励和预测性属性进行加工，以及在多大程度上 神经化学物质多巴胺参与其中。为此，我们将使用活体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，当出现在这些实验中时，VP和NAcc神经元对激励属性的反应比对奖励线索的预测性属性更敏感。

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.