NEUROBIOLOGY OF BINGE-TYPE BEHAVIOR

暴饮暴食行为的神经生物学

• 批准号: 7185103
• 负责人: REBECCA L CORWIN
• 金额: $ 30.15万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-12 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7185103
• 关键词: Address; Affect; Agonist; Baclofen; Behavior; Behavioral; Brain; Brain region; Condition; Consumption; Corpus striatum structure; Data; Disease; Dose; Eating; Eating Disorders; Estrous Cycle; Fatty acid glycerol esters; Female; Food deprivation (experimental); GABA-B Receptor; Galanin; Health; Human; Intake; Investigation; Laboratories; Ligands; Mediating; Neurobiology; Neurologic; Obesity; Ovarian hormone; Peptides; Peripheral; Pharmaceutical Preparations; Procedures; Protocols documentation; Publishing; Rattus; Reporting; Research; Role; Self Administration; Signal Transduction; Site; Substance abuse problem; Substantia nigra structure; Testing; Thinking; Time; Ursidae Family; Ventral Tegmental Area; Week; Work; binge type behavior; dosage; drug of abuse; excessive behavior; feeding; insight; male; procolipase; receptor density; sex

DESCRIPTION (provided by applicant): Neurological mechanisms relevant to intermittent episodes of behavioral excess are not well understood, but bear investigation due to the contribution of this kind of behavior to health problems such as disordered eating, obesity and substance abuse. We have developed a unique rat bingeing protocol, which we have been using to examine the neurobiology associated with repeated intermittent excessive fat intake that is maintained over extended periods of time. Peptides that regulate fat intake under non-binge conditions are without effect when rats binge on fat. In contrast, recent results from my laboratory show that the GABA-B agonist baclofen reduces fat intake in our protocol, while having no effect in non-bingeing protocols. Others have reported that baclofen reduces self-administration of abused drugs. This suggests that the neurobiology of bingeing is different from that of non-binge behavior, but may share similarities with the neurobiology of substance abuse. Therefore, we will use baclofen to test the overall hypothesis guiding this research, i.e. that GABA-B receptors have a role in binge-type eating. The following Specific Aims will be addressed: AIM 1: To test the hypothesis that GABA-B ligands will differentially affect fat consumption in bingeing and non-bingeing rats. Hypotheses: a) Lower dosages of baclofen will reduce food intake to a greater extent in bingeing rats than in non-bingeing rats; Lower dosages of baclofen will reduce food intake to a greater extent in females than in males; b) Baclofen-induced reductions in binge intake will be mediated centrally; GABA-B receptor blockade will stimulate binge intake; c) Dosages of GABA-B ligands that affect food intake will not affect general behavioral activity in the bingeing rats. AIM 2: To test the hypothesis that baclofen-induced reductions in fat intake are enhanced with repeated bingeing. Hypothesis: Lower dosages of baclofen will reduce food intake to a greater extent in rats that have repeatedly binged than in rats that have engaged in fewer binge episodes. AIM 3: To test the hypothesis that the VTA is a sensitive site of action for baclofen-induced reductions in bingeing. Hypothesis: Lower doses of baclofen will reduce bingeing when infused into the VTA than when infused into the striatum or substantia nigra. These studies are the first to examine the contribution of GABA-B receptors to bingeing and will provide new insight into the neurobiology of bingeing-related disorders

描述（由申请人提供）：与间歇性行为过度发作相关的神经机制尚未得到很好的理解，但由于这种行为对饮食失调、肥胖和药物滥用等健康问题的影响，需要进行调查。我们开发了一种独特的大鼠暴食方案，我们一直在使用该方案来研究与长时间维持的重复间歇性过量脂肪摄入相关的神经生物学。在非暴饮暴食条件下调节脂肪摄入的肽在大鼠暴饮暴食时没有效果。相比之下，我实验室最近的结果表明，GABA-B激动剂巴氯芬在我们的方案中减少了脂肪摄入，而在非暴饮暴食方案中没有效果。其他人报告说，巴氯芬减少滥用药物的自我管理。这表明暴食的神经生物学不同于非暴食行为，但可能与物质滥用的神经生物学有相似之处。因此，我们将使用巴氯芬来检验指导这项研究的总体假设，即GABA-B受体在暴食型饮食中发挥作用。以下具体目标将被解决：目的1：为了测试的假设，GABA-B配体将不同的影响脂肪消耗在暴食和非暴食大鼠。假设：a）较低剂量的巴氯芬将在暴食大鼠中比在非暴食大鼠中更大程度地减少食物摄入;较低剂量的巴氯芬将在雌性大鼠中比在雄性大鼠中更大程度地减少食物摄入; B）巴氯芬诱导的暴食摄入的减少将由中枢介导; GABA-B受体阻断将刺激暴食摄入; c）影响食物摄入的GABA-B配体的剂量不会影响暴食大鼠的一般行为活动。目的2：验证反复暴饮暴食会增强Baclidine诱导的脂肪摄入减少的假设。假设：低剂量的巴氯芬将在更大程度上减少反复暴饮暴食的大鼠的食物摄入量，而不是较少暴饮暴食的大鼠。目的3：验证腹侧被盖区是减少暴食的一个敏感作用部位的假设。假设：与注入纹状体或黑质相比，注入腹侧被盖区时，较低剂量的巴氯芬将减少暴食。这些研究是第一次检查GABA-B受体对暴食的贡献，并将为暴食相关疾病的神经生物学提供新的见解