Regulation of Amphetamine Reward by Central Insulin

中枢胰岛素对安非他明奖励的调节

• 批准号: 6797957
• 负责人: Joy Hao
• 金额: $ 3.97万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-20 至 2005-09-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6797957
• 关键词: amphetamines; behavior test; bioenergetics; body weight; brain electrical activity; central nervous system stimulants; cerebrospinal fluid; dietary restriction; drug delivery systems; histology; hormone regulation /control mechanism; hormone therapy; insulin; laboratory rat; nutrition related tag; pharmacology; predoctoral investigator; protease inhibitor; psychopharmacology; radioimmunoassay; reinforcer; stereotaxic techniques; substance abuse related behavior; substance abuse related disorder

DESCRIPTION (provided by applicant): Basic and clinical research indicate a close association between ingestive behavior and drug-seeking. This laboratory has shown that sustained negative energy balance augments behavioral and cellular effects of psychostimulants. A key endocrine response to negative energy balance is hypoinsulinemia, evident in both plasma and cerebrospinal fluid (CSF). The objective of this proposal is to determine whether central insulin replacement, as delivered by osmotic minipumps, prevents the augmentation of amphetamine effects in chronically food-restricted rats. The first aim is to determine if the output of the minipump remains stable throughout a 14-day period, and whether addition of an anti-aggregant or protease inhibitor helps to maintain delivery of the intended dose. The second aim is to determine the dose of insulin that restores CSF insulin level of food-restricted rats to the control level, as measured by CSF sampling and radioimmunoassay. The third and fourth aims are to determine if intracerebroventricular insulin replacement during food restriction reverses the augmentation of amphetamine's stimulant and rewarding effects. Stimulant effects are measured using photobeam interruption to count horizontal and vertical movements. Rewarding effects are measured by the degree of threshold-lowering for electrical brain stimulation reward. Results of this research may shed light on the high comorbidity of drug abuse and eating disorders.

描述（由申请人提供）： 基础和临床研究表明，发芽行为与寻求药物之间的密切关联。 该实验室表明，持续的负能量平衡增加了心理刺激物的行为和细胞影响。对负能量平衡的关键内分泌反应是低胰岛素血症，在血浆和脑脊液（CSF）中都明显。该提案的目的是确定中央胰岛素的替代是通过渗透微型植物传递的，可以防止在慢性食品限制的大鼠中增加苯丙胺作用的增强。第一个目的是确定在14天的时间内，微型机的输出是否保持稳定，以及添加抗药物或蛋白酶抑制剂是否有助于维持预期剂量的递送。第二个目的是确定胰岛素的剂量，该胰岛素通过CSF采样和放射免疫测定法测量，将CSF胰岛素水平恢复到控制水平。第三和第四的目的是确定食物限制期间脑室内胰岛素的替代是否会逆转苯丙胺刺激剂的增强和有益的作用。使用Photobeam中断来测量刺激效应，以计算水平和垂直运动。奖励效果是通过低阈值降低的程度来衡量的，用于电脑刺激奖励。这项研究的结果可能阐明了药物滥用和饮食失调的高度合并症。