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

总结： 酒精使用障碍（AUD）给现代社会带来了重大的社会和经济负担。值得注意的是， 在酒精中毒患者中观察到的受损的生理和代谢状态对治疗产生不利影响 结果。此外，许多酗酒者营养不良，由此造成的营养缺乏可能 会导致酒精中毒然而，营养作为一种重要的治疗方法往往被忽视 元为AUD。我们的初步数据表明，模式喂养（由间歇性 营养完全可口饮食（NPD），一种不影响体重的治疗 或组合物，在非依赖性啮齿动物中诱导抗焦虑行为并减少酒精摄入， 在AUD的管理中具有重要的临床意义。然而，关键的第一步包括 确定这种饮食干预是否能成功地调节临床前模型中的酒精摄入 的AUD。解决这些关键问题对于理解营养不良的作用非常重要。 调节与这种多方面疾病相关的各种症状的状态。大鼠的P线已显示 为了显示建议的标准（例如，自愿过度和复发性饮酒和出现 慢性酒精暴露后的酒精依赖）被认为是合适的动物模型， 学习AUD本申请的目的是评估过度和复发性酒精消费， 酒精偏好（P）和非偏好（NP）大鼠在模式化喂养NPD后。另外我们 还将确定潜在的行为和神经生物学机制介导的影响， 喂养范例目的1将研究NPD模式喂养对非依赖性过度和 类似复发的饮酒行为目标2将评估类似的饮食方法对酒精的影响 依赖引起的负面情绪状态，酒精摄入量增加和神经生物学变化， 皮质-纹状体回路目的3将研究内侧前额叶皮层（mPFC）神经降压素信号的作用 调节NPD对饮酒的影响。中心预测是NPD的模式化喂养 在AUD啮齿动物模型中减弱有问题的酒精消费和负面情绪状态， 募集mPFC神经降压素信号。这一假设得到了我们的初步数据和工作的支持。 他人治疗酒精性疾病中存在的代谢缺陷是一个重要的概念创新 因为目前批准的方法都没有针对与这些疾病相关的改变的营养和情绪状态 关于AUD除了恢复营养不足，暴露于NPD也可以恢复情绪 国家从而加强其他行为和药理学策略的管理酗酒 这将有助于禁欲

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.