The Impact of Patterned Feeding of a Palatable Diet on Excessive Alcohol Drinking

美味饮食的模式喂养对过量饮酒的影响

• 批准号: 10087942
• 负责人: Sunil Sirohi
• 金额: $ 10.65万
• 依托单位: XAVIER UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10087942
• 关键词: Abstinence; Address; Adolescent; Adult; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcoholism; Alcohols; Animal Model; Anti-Anxiety Agents; Attenuated; Behavior; Behavioral; Behavioral Mechanisms; Body Composition; Body Weight; Brain; Calories; Chronic; Clinical; Corpus striatum structure; Data; Diagnosis; Diet; Diet and Nutrition; Dietary Intervention; Disease; Drug Addiction; Economic Burden; Emotional; Exposure to; Face; Feeding Patterns; Food; Genetic; Goals; Heavy Drinking; Impairment; Intake; Knowledge; Malnutrition; Medial; Mediating; Metabolic; Metabolic Control; Modernization; Neurobiology; Neurotensin; Neurotensin Receptors; Nutrient; Nutritional; Nutritional status; Palate; Pathology; Pathway interactions; Patients; Pattern; Peptides; Pharmacology; Physiological; Pre-Clinical Model; Prefrontal Cortex; Prevalence; Principal Investigator; Public Health; Rattus; Receptor Signaling; Recovery; Relapse; Rodent; Rodent Model; Role; Signal Transduction; Site; Societies; Study models; Testing; Therapeutic; Treatment outcome; Ultrasonics; United States; Work; alcohol abuse therapy; alcohol consequences; alcohol exposure; alcohol sensitivity; alcohol use disorder; anxiety-like behavior; associated symptom; behavioral pharmacology; dietary approach; drinking behavior; drug of abuse; feeding; improved; innovation; negative affect; negative emotional state; neurobiological mechanism; neuropsychiatric disorder; nutrition; pre-clinical; problem drinker; protein expression; recruit; reinforced behavior; reward circuitry; social; therapeutic target; therapeutically effective; vocalization

Summary: Alcohol use disorder (AUD) presents a significant social and economic burden to modern society. Notably, impaired physiological and metabolic status observed in alcoholic patients adversely affects treatment outcome. Furthermore, many alcoholics are malnourished and resultant nutritional deficiencies may contribute to the pathology of alcoholism. However, nutrition is often overlooked as an important treatment component for AUD. Our preliminary data indicate that a patterned feeding (produced by an intermittent availability) of a nutritionally complete palatable diet (NPD), a treatment that does not influence body weight or composition, induces anxiolytic behavior and attenuates alcohol intake in non-dependent rodents, which has important clinical implications in the management of AUD. However, a critical first step involves determining if such dietary intervention would be successful in regulating alcohol intake in preclinical models of AUD. Addressing these critical questions is important to understand the role of compromised nutritional status in regulating various symptoms associated with this multifaceted disorder. P-line of rats has been shown to display proposed criteria (e.g., voluntary excessive and relapse-like alcohol drinking and the emergence of alcohol dependence following chronic alcohol exposure) to be considered as a suitable animal model for studying AUD. The objective of this application is to evaluate excessive and relapse-like alcohol consumption in the alcohol-preferring (P) and non-preferring (NP) rats following patterned feeding of NPD. In addition, we will also determine the underlying behavioral and neurobiological mechanisms mediating the effects of our feeding paradigm. Aim 1 will examine the impact of patterned feeding of NPD on non-dependent excessive and relapse-like alcohol drinking behavior. Aim 2 will evaluate the effect of a similar dietary approach on alcohol dependence-induced negative emotional states, escalated alcohol intake and neurobiological changes in the cortico-striatal circuitry. Aim 3 will examine the role of medial prefrontal cortex (mPFC) neurotensin signaling in regulating effects of NPD on alcohol drinking. The central prediction is that patterned feeding of NPD attenuates problematic alcohol consumption and negative emotional states in rodent’s models of AUD by recruiting mPFC neurotensin signaling. This hypothesis is supported by our preliminary data and work of others. Treating metabolic deficiencies present in the alcoholic condition is a significant conceptual innovation as none of the currently approved approaches target both altered nutritional and emotional states associated with AUD. In addition to restoring nutritional deficits, exposure to NPD could also serve to restore emotional state thereby enhancing other behavioral and pharmacological strategies for the management of alcoholism which will facilitate the pathway to abstinence.

摘要： 酒精使用障碍给现代社会带来了巨大的社会和经济负担。值得注意的是， 酒精中毒患者的生理和代谢状态受损对治疗有不利影响 结果。此外，许多酗酒者营养不良，由此导致的营养缺乏可能 对酒精中毒的病理有贡献。然而，营养作为一种重要的治疗手段往往被忽视。 用于澳元的组件。我们的初步数据表明，一种模式进食(由间歇性 可得性)营养全面的可口饮食(NPD)，一种不影响体重的治疗 或成分，诱导非依赖啮齿动物的焦虑行为并减少酒精摄取，这 对AUD的治疗具有重要的临床意义。然而，关键的第一步包括 在临床前模型中确定这种饮食干预在调节酒精摄入量方面是否成功 澳元。解决这些关键问题对于理解营养不良的作用很重要 在调节与这种多方面疾病相关的各种症状方面的地位。已经显示了大鼠的P线 展示拟议的标准(例如，自愿过量饮酒和反复饮酒以及出现 慢性酒精暴露后的酒精依赖)被认为是一种合适的动物模型 学习澳元。这个应用程序的目标是评估过度和复发的酒精消费在 酒精嗜好(P)和非嗜酒(NP)大鼠按模式喂饲NPD。此外，我们 也将决定潜在的行为和神经生物学机制，这些机制介导了我们的 喂食范例。目标1将研究NPD的模式喂养对非依赖型过度和 故态型饮酒行为。目标2将评估类似的饮食方法对酒精的影响 依赖诱导的负面情绪状态、酒精摄入量增加和神经生物学变化 皮质-纹状体环路。目标3将研究内侧前额叶皮质(MPFC)神经降压素信号的作用 在调节NPD对饮酒的影响方面。中心预测是NPD的模式化喂养 通过以下方式减轻AUD啮齿动物模型中有问题的酒精消费和负面情绪状态 招募mPFC神经降压素信号。这一假设得到了我们的初步数据和以下工作的支持 其他。治疗酗酒状态下的代谢缺陷是一项重大的理念创新 因为目前批准的方法中没有一种既针对改变的营养状态又针对相关的情绪状态 用澳元。除了恢复营养不足，接触NPD还可以帮助恢复情绪 从而加强管理酒精中毒的其他行为和药理学策略 这将使禁欲之路更加便利。