Affective neuroscience of taste reactivity

描述(由申请者提供)：积极情绪障碍是快感缺乏、烦躁不安和其他积极情绪的问题--从抑郁到成瘾再到精神分裂症。在正常的日常生活中，情感反应是幸福所必需的。要解释为什么积极的情绪会在情绪障碍中出错，首先必须了解大脑系统是如何正常地对愉快的事件产生积极的情感反应(喜欢)。然而，关于大脑是如何对奖励做出正常的“喜欢”反应的，我们知之甚少。这个项目将研究大脑的“享乐热点”(能够放大“喜欢”的立方毫米区域)，这些热点会对典型的奖励--甜蜜--产生积极的情感反应。 该项目将研究伏隔核和腹侧苍白球中的阿片和内源性大麻类享乐性热点，这些热点是享乐性“喜欢”反应和激励性“想要”自然食物奖励的基础。该项目将结合显微注射技术与绘制人类和啮齿动物共有的自然同源“喜欢”反应(味觉反应范式)的功能定位和测量的程序。据预测，Mu阿片和CB1类内源性大麻素机制在伏隔核内侧壳和腹侧苍白球中共享相同的立方毫米享乐热点，不同的伏隔-苍白球回路可以为相同的奖励而调节“喜欢”或“想要”。 结果应该揭示边缘热点内增强享乐反应的机制的重要特征。它还将揭示同样的大脑机制在产生普通水平的积极情绪以及在饥饿等调节享乐影响的食欲状态中所扮演的正常角色。总而言之，这些结果将提供有关神经系统的有价值的信息，这些神经系统会对自然奖励产生积极影响。更好地理解大脑是如何产生积极情绪的，应该会为饮食失调、成瘾、抑郁、精神分裂症和其他情绪障碍所涉及的积极情绪的破坏提供有用的见解和最终改进的治疗方法。

DESCRIPTION (provided by applicant): Disruption of positive affect is a problem in anhedonia, dysphoria and other emotional Positive pathologies ranging from depression to addiction to schizophrenia. affective reaction is needed for well-being in normal daily life. To interpret why positive affect goes wrong  in emotional disorders it is first necessary to understand how brain systems  normally generate positive affective reactions to pleasant events ('liking'). Yet little is known about how brains generate normal 'liking' reactions to rewards. This project will study brain 'hedonic hotspots' (cubic-millimeter sites able to magnify 'liking') that generate positive affective reactions to a prototypical reward, sweetness. The project will study opioid and endocannabinoid hedonic hotspots in the nucleus accumbens and ventral pallidum that underlie hedonic 'liking' reactions and motivational 'wanting' for natural food reward. The project will combine microinjection techniques with procedures for mapping localization of function and measures of natural homologous 'liking' reactions shared by humans and rodents (taste reactivity paradigm). Predictions are that mu opioid and CB1 endocannabinoid mechanisms share same cubic-millimeter hedonic hotspots in medial shell of nucleus accumbens and in ventral pallidum, and that different accumbens-pallidum circuits can mediate 'liking' versus 'wanting' for the same reward. Results should reveal important features of mechanisms within limbic hotspots that enhance hedonic reactions above normal. It will also reveal the normal roles of those same brain mechanisms in generating ordinary levels of positive affect, and in appetite states such as hunger that modulate hedonic impact. Altogether, the results will provide valuable information about the neural systems that generate positive affect for natural reward. Improved understanding of how brains generate positive affect should provide useful insights and eventual improvements in treatment for the disruption of positive affect involved in eating disorders, addiction, depression, schizophrenia and other mood disorders.