Rodriguez Francisco D, Coveñas Rafael
Department of Biochemistry and Molecular Biology, Group GIR-BMD, Faculty of Chemistry, University of Salamanca, 37001 Salamanca. Spain.
Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, University of Salamanca, 37007 Salamanca. Spain.
Curr Med Chem. 2017;24(23):2528-2558. doi: 10.2174/0929867324666170316120836.
The term Alcohol Use Disorder (AUD) incorporates different states of disease related to the recurrent use of alcohol and linked to the relevant impairment, disability and failure to perform major responsibilities in different realms. Many neurotransmitter systems are involved in the phases or states of alcoholism from reward mechanisms, associated to binge intoxication, to stress and anxiety linked to relapse and withdrawal. Some neuropeptides play a key function in the control of anxiety and stress, and establish a close relationship with the pathological mechanisms underlying alcohol addiction. Among them, Neuropeptide Y (NPY), Corticotropin-releasing factor (CRF)/Urocortins and Neuropeptide S (NPS) cross-talk, and are responsible for some of the maladaptation processes that the brain exhibits during the progression of the disease.
In this study, we review the literature mainly focused on the participation of these neuropeptides in the pathophysiology of AUD, as well as on the use of antagonists designed to investigate signaling mechanisms initiated after ligand binding and their connection to biochemical adaptation events coupled to alcohol addiction. The possibility that these systems may serve as therapeutic objectives to mitigate or eliminate the harm that drinking ethanol generates, is also discussed.
The peptide systems reviewed here, together with other neurotransmitter systems and their mutual relationships, are firm candidates to be targeted to treat AUD.
酒精使用障碍(AUD)这一术语涵盖了与反复饮酒相关的不同疾病状态,并与不同领域的相关损害、残疾以及无法履行主要职责有关。从与暴饮中毒相关的奖赏机制到与复发和戒断相关的压力和焦虑,许多神经递质系统都参与了酗酒的各个阶段或状态。一些神经肽在焦虑和压力的控制中发挥关键作用,并与酒精成瘾的病理机制建立密切关系。其中,神经肽Y(NPY)、促肾上腺皮质激素释放因子(CRF)/尿皮质素和神经肽S(NPS)相互作用,并且在疾病进展过程中大脑所表现出的一些适应不良过程中起作用。
在本研究中,我们回顾了主要关注这些神经肽在酒精使用障碍病理生理学中的作用的文献,以及旨在研究配体结合后启动的信号传导机制及其与酒精成瘾相关生化适应事件的联系的拮抗剂的使用情况。还讨论了这些系统作为减轻或消除饮用乙醇所产生危害的治疗靶点的可能性。
本文所综述的肽系统,连同其他神经递质系统及其相互关系,是治疗酒精使用障碍的有力候选靶点。