Striatal Acetylcholine-Opioid Interactions and Feeding

描述（由申请人提供）：目前肥胖症的“流行病”在世界范围内是一个日益严重的问题。寻找长期治疗是一个持续的过程，迄今为止，重点关注稳态因素，特别是下丘脑。拟议的研究旨在解决纹状体乙酰胆碱系统和阿片系统之间可能的相互作用与食物摄入量。我们的初步研究结果表明，纹状体内注射毒蕈碱拮抗剂东莨菪碱产生长期的食物摄入量减少和阿片类药物诱导的摄食反应脱敏。在目前的建议中，我们将探讨东莨菪碱治疗影响的各种行为和神经药理学参数。将进行时程研究，以确定东莨菪碱厌食症的持续时间，进一步的实验将检查东莨菪碱诱导的改变，在不同的动机状态和其他纹状体神经递质系统的调制。除这些实验外，还将沿着神经药理学试验进行东莨菪碱从纹状体清除的药代动力学研究，以评估纹状体内阿片受体的功能。与公共卫生的相关性：在这项建议中概述的工作有可能确定一个新的神经药理学途径控制进食。这可能会导致控制食欲的新药，这可能有助于缓解肥胖症的流行。

DESCRIPTION (provided by applicant): The current "epidemic" of obesity is an increasing problem in societies world wide. The search for a long term treatment is an ongoing process with much focus to date on homeostatic factors, particularly in the hypothalamus. The proposed research is designed to address a possible interaction between the striatal acetylcholine system and opioid system with regard to food intake. Our preliminary results indicate that intrastriatal infusions of the muscarinic antagonist scopolamine produce a long-term reduction on food intake and a desensitization of opioid-induced feeding responses. In the current proposal, we will explore various behavioral and neuropharmacological parameters affected by scopolamine treatment. A time course study will be conducted to determine the duration of scopolamine anorexia and further experiments will examine scopolamine-induced alterations in different motivational states and modulation of other striatal neurotransmitter systems. In addition to these experiments, a pharmacokinetic study of scopolamine clearance from striatum will be performed along with neuropharmacological assays to assess the function of the opioid receptor inside the striatum. Relevance to public health: The work outlined in this proposal has the potential to identify a novel neuropharmacological pathway in the control of feeding. This could lead to new drugs for appetitive control, which could help alleviate the obesity epidemic.