Department of Biochemistry and Molecular Biology, Faculty of Chemical Sciences, University of Salamanca, 37008 Salamanca, Spain.
Group GIR-USAL: BMD (Bases Moleculares del Desarrollo), University of Salamanca, 37008 Salamanca, Spain.
Int J Mol Sci. 2023 May 12;24(10):8656. doi: 10.3390/ijms24108656.
Harmful alcohol use is responsible for a group of disorders collectively named alcohol use disorders (AUDs), according to the DSM-5 classification. The damage induced by alcohol depends on the amount, time, and consumption patterns (continuous and heavy episodic drinking). It affects individual global well-being and social and familial environments with variable impact. Alcohol addiction manifests with different degrees of organ and mental health detriment for the individual, exhibiting two main traits: compulsive drinking and negative emotional states occurring at withdrawal, frequently causing relapse episodes. Numerous individual and living conditions, including the concomitant use of other psychoactive substances, lie in the complexity of AUD. Ethanol and its metabolites directly impact the tissues and may cause local damage or alter the homeostasis of brain neurotransmission, immunity scaffolding, or cell repair biochemical pathways. Brain modulator and neurotransmitter-assembled neurocircuitries govern reward, reinforcement, social interaction, and consumption of alcohol behaviors in an intertwined manner. Experimental evidence supports the participation of neurotensin (NT) in preclinical models of alcohol addiction. For example, NT neurons in the central nucleus of the amygdala projecting to the parabrachial nucleus strengthen alcohol consumption and preference. In addition, the levels of NT in the frontal cortex were found to be lower in rats bred to prefer alcohol to water in a free alcohol-water choice compared to wild-type animals. NT receptors 1 and 2 seem to be involved in alcohol consumption and alcohol effects in several models of knockout mice. This review aims to present an updated picture of the role of NT systems in alcohol addiction and the possible use of nonpeptide ligands modulating the activity of the NT system, applied to experimental animal models of harmful drinking behavior mimicking alcohol addiction leading to health ruin in humans.
有害的酒精使用是一组被称为酒精使用障碍（AUDs）的疾病的原因，根据 DSM-5 分类。酒精引起的损害取决于数量、时间和消费模式（连续和重度间歇性饮酒）。它影响个人的整体幸福感和社会及家庭环境，影响程度不同。酒精成瘾表现为个体不同程度的器官和心理健康损害，表现出两个主要特征：强迫性饮酒和戒断时出现的负面情绪状态，经常导致复发发作。许多个人和生活条件，包括同时使用其他精神活性物质，都存在 AUD 的复杂性。乙醇及其代谢物直接影响组织，并可能导致局部损伤或改变大脑神经递质传递、免疫支架或细胞修复生化途径的内稳态。大脑调节剂和神经递质组装的神经回路以相互交织的方式控制奖励、强化、社交互动和酒精行为的消费。实验证据支持神经降压素（NT）在酒精成瘾的临床前模型中的参与。例如，投射到臂旁核的杏仁核中央核中的 NT 神经元增强了酒精的消耗和偏好。此外，与野生型动物相比，在自由选择酒精-水的情况下，更喜欢酒精而不是水的大鼠的前额皮质中的 NT 水平较低。NT 受体 1 和 2 似乎参与了几种敲除小鼠模型中的酒精消耗和酒精作用。本综述旨在介绍 NT 系统在酒精成瘾中的作用的最新图片，以及可能使用调节 NT 系统活性的非肽配体，应用于模拟导致人类健康受损的酒精成瘾的有害饮酒行为的实验动物模型。
