Mu-opioid systems in the prefrontal cortex: role in appetitive behavior

描述（由申请人提供）：有人认为世界各地的肥胖率已达到流行病的程度。与这种威胁相关的是与肥胖有关的后遗症，如患2型糖尿病、心脏病和中风的风险增加。考虑到这些统计数据，研究了解参与调节体重和食物摄入相关行为的系统是至关重要的。在我们对基本食欲行为的“高阶”皮层控制的理解上有一个显著的差距。为了解决这一差距，我们建议探索内侧前额叶皮层，这是一个与“下游”区域联系丰富的区域，介导进食行为的稳态和享乐控制。与这一目标特别相关的是，我们实验室的初步结果表明，刺激mPFC中的mu-阿片受体增加了食物剥夺和非食物剥夺动物的食物摄入，并促进了极端的多动和运动循环的分裂。令人惊讶的是，关于PFC阿片类药物的功能作用知之甚少，很少有研究检查局部PFC阿片类药物操作后的行为影响。因此，我们建议探索这些效应背后的神经药理学和解剖学基础，并研究我们观察到的效应背后的精确行为结构。

DESCRIPTION (provided by applicant): It has been suggested that obesity rates around the world are at epidemic proportions. Relevant to this threat are the sequelae that are associated with obesity, such as increased risk of developing type 2 diabetes, heart disease, and stroke. With these statistics in mind, research into understanding the systems that are involved in regulating body weight and food intake-associated behaviors is critical. There is a notable gap in our understanding of "higher-order" cortical control of basic appetitive behaviors. To address this gap, we propose to explore the medial prefrontal cortex, an area rich in connections to 'downstream' regions that mediate homeostatic and hedonic control of feeding behavior. Particularly germane to this goal are preliminary results from our lab showing that stimulation of mu-opioid receptors in the mPFC augments food intake in both food- deprived and non-deprived animals, and promotes extreme hyperactivity and fragmentation of motor repetoires. Surprisingly, very little is known about the functional role of PFC opioids and very few studies have examined the behavioral effects following local PFC opioid manipulation. Thus, we propose to explore the neuropharmacology and anatomical substrates underlying these effects, and to investigate the precise behavioral constructs underlying our observed effects. PUBLIC HEALTH RELEVANCE: The work outlined in this proposal has the potential to enhance our understanding of how higher-order cognitive factors impinge upon, and perhaps organize and regulate, basic homeostatic mechanisms related to food intake. Hence, this work could lead to novel and exciting insights into the 'top-down' executive control of basic motivational and homeostatic processes. The proposed work may also elucidate important new knowledge regarding peptide control of prefrontal cortical function, which could have profound translational implications for disorders like ADHD and Schizophrenia.