Striatal Acetylcholine-Opioid Interactions and Feeding

纹状体乙酰胆碱-阿片类药物相互作用和喂养

• 批准号: 7739448
• 负责人: Michelle L Perry
• 金额: $ 4.12万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-11-01 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739448
• 关键词: Acetylcholine; Address; Affect; Animals; Anorexia; Attention; Autoradiography; Behavioral; Binding; Biological Assay; Biological Process; Corpus striatum structure; Coupling; Desire for food; Diet; Drug Kinetics; Eating; Epidemic; Experimental Water Deprivation; Fatty acid glycerol esters; Feeding behaviors; Food; Food deprivation (experimental); G Protein-Coupled Receptor Genes; GTP-Binding Proteins; Glutamates; Goals; Homeostasis; Hour; Hypothalamic structure; Infusion procedures; Knowledge; Laboratories; Lead; Mediating; Metabolic; Motivation; Motor; Motor Activity; Muscarinic Acetylcholine Receptor; Muscarinic Antagonists; Muscarinics; Neurotransmitters; Nucleus Accumbens; Obesity; Opioid; Opioid Receptor; Pathway interactions; Pharmaceutical Preparations; Plastics; Play; Process; Proteins; Public Health; Research; Rewards; Role; Scopolamine; Site; Societies; Specificity; System; Testing; Time; Tissues; Ventral Striatum; Work; base; behavior test; desensitization; design; feeding; food consumption; hedonic; novel; receptor function; relating to nervous system; research study; response

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.

描述（由申请人提供）：肥胖的当前“流行病”是全世界社会的越来越多的问题。寻找长期治疗是一个正在进行的过程，迄今为止，迄今为止，尤其是在下丘脑中，重点是稳态因素。拟议的研究旨在解决纹状体乙酰胆碱系统与阿片类药物系统在食物摄入方面的可能相互作用。我们的初步结果表明，毒蕈碱拮抗剂Scopolamine的纹状体内输注可长期降低食物摄入量和阿片类药物诱导的喂养反应的脱敏。在当前的提案中，我们将探讨受西侧治疗影响的各种行为和神经药理学参数。将进行一项时间课程研究，以确定Scopolamine厌食症的持续时间，进一步的实验将检查Scopolamine诱导的不同动机状态的变化以及其他纹状体神经递质系统的调节。除这些实验外，还将与纹状体清除的药代动力学研究以及神经药理学分析一起评估纹状体内阿片类受体的功能。与公共卫生的相关性：该提案中概述的工作有可能在控制喂养方面识别一种新型的神经药理学途径。这可能会导致食欲控制的新药物，这可能有助于减轻肥胖症的流行。