Mapping of Nucleus Accumbens Afferents and Efferents Mediating Opioid-Induced Feeding

生物体在不同的环境下进行取食行为。这些措施包括自发摄入量、调节体重和应对诸如食物匮乏或葡萄糖或脂肪能源丧失等动态平衡挑战的摄入量。摄入量的增加也与食物的可口、享乐或味道有关。大脑中的内源性阿片肽(脑啡肽、内啡肽)及其受体(Mu、Delta和Kappa)与刺激这些不同类型的摄食行为密切相关。特定的大脑部位，包括伏隔核和腹侧被盖区，是阿片激动剂刺激摄食行为以及调节其他奖赏和成瘾行为的地方。先进的神经解剖学和神经化学技术已经绘制出连接这些大脑区域的内在神经回路以及与控制摄食行为的感觉和监控区的外部联系。本方案的目标是通过使用选择性的u和Delta阿片激动剂来刺激摄食，系统地研究伏隔核和腹侧被盖区内和之间的这些受体底物，然后确定其他特定神经化学受体(阿片、多巴胺、GABA、兴奋性氨基酸)的药理拮抗剂是否阻止这些反应。这种方法将大脑内调节摄食的特定神经解剖和神经化学回路识别为重要的享乐和稳态反应，并对理解奖赏和成瘾具有潜在的意义

Organisms engage in feeding behavior under different circumstances. These include spontaneous intake regulating body weight and intake in reponse to such homeostatic challenges as food deprivation or the loss of glucose or fat energy sources. Intake increases also occur in relation to palatable, hedonic or taste qualities of the food. Endogenous opioid peptides (enkephalins, endorphins) and their receptors (mu, delta and kappa) in the brain are intimately involved in stimulating these different types of feeding behavior. Specific brain sites, including the nucleus accumbens and ventral tegmental area, are places where opioid agonists stimulate feeding behavior as well as mediate other reward and addictive behaviors. Advanced neuroanatomical and neurochemical techniques have mapped the intrinsic neuronal circuitry interconnecting these brain areas as well as extrinsic connections with sensory and montor areas controlling feeding behavior.The goals of this proposal are to systematically study these receptor substrates within and between the nucleus accumbens and ventral tegmental area by using selective mu and delta opioid agonists to stimulate feeding, and then determine whether pharmacological anatagonists of other specific neurochemical receptors (opioid, dopamine, GABA, excitatory amino acids) block these responses.This approach identifies specific neuroanatomical and neurochemical circuits within the brain mediating feeding as an important hedonic and homeostatic response as well as having potential implications for the understanding of reward and addiction