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

生物体在不同的环境下进行摄食行为。 这些包括调节体重的自发摄入和响应于诸如食物剥夺或葡萄糖或脂肪能量来源的损失的稳态挑战的摄入。 摄入量的增加也与食物的可口性、享乐性或味道品质有关。 大脑中的内源性阿片肽（脑啡肽，内啡肽）及其受体（μ，δ和κ）密切参与刺激这些不同类型的进食行为。 特定的大脑部位，包括延髓核和腹侧被盖区，是阿片受体激动剂刺激进食行为以及介导其他奖励和成瘾行为的地方。 先进的神经解剖学和神经化学技术已经绘制出了这些脑区之间的内在神经元回路以及与控制摄食行为的感觉和监控区之间的外在联系，本研究的目的是系统地研究这些受体底物，并通过选择性μ和δ阿片受体激动剂刺激摄食，然后确定其他特定神经化学受体的药理学拮抗剂（阿片类，多巴胺，GABA，兴奋性氨基酸）这种方法确定了大脑内特定的神经解剖学和神经化学回路，这些回路介导进食作为一种重要的享乐和稳态反应，并对大脑的发育具有潜在的影响。对奖赏和成瘾的理解

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