Schimmer Jonas, Patwell Ryan, Küppers Stephanie, Grinevich Valery
Department of Neuropeptide Research in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Curr Top Behav Neurosci. 2023 Sep 12. doi: 10.1007/7854_2023_444.
The hypothalamic neuropeptide oxytocin (OT) is well known for its prosocial, anxiolytic, and ameliorating effects on various psychiatric conditions, including alcohol use disorder (AUD). In this chapter, we will first introduce the basic neurophysiology of the OT system and its interaction with other neuromodulatory and neurotransmitter systems in the brain. Next, we provide an overview over the current state of research examining the effects of acute and chronic alcohol exposure on the OT system as well as the effects of OT system manipulation on alcohol-related behaviors in rodents and humans. In rodent models of AUD, OT has been repeatedly shown to reduce ethanol consumption, particularly in models of acute alcohol exposure. In humans however, the results of OT administration on alcohol-related behaviors are promising but not yet conclusive. Therefore, we further discuss several physiological and methodological limitations to the effective application of OT in the clinic and how they may be mitigated by the application of synthetic OT receptor (OTR) agonists. Finally, we discuss the potential efficacy of cutting-edge pharmacology and gene therapies designed to specifically enhance endogenous OT release and thereby rescue deficient expression of OT in the brains of patients with severe forms of AUD and other incurable mental disorders.
下丘脑神经肽催产素（OT）因其对包括酒精使用障碍（AUD）在内的各种精神疾病具有亲社会、抗焦虑和改善作用而广为人知。在本章中，我们将首先介绍OT系统的基本神经生理学及其与大脑中其他神经调节和神经递质系统的相互作用。接下来，我们概述了当前研究的现状，这些研究考察了急性和慢性酒精暴露对OT系统的影响，以及OT系统操纵对啮齿动物和人类与酒精相关行为的影响。在AUD的啮齿动物模型中，OT已被反复证明可减少乙醇消耗，尤其是在急性酒精暴露模型中。然而，在人类中，OT给药对与酒精相关行为的影响虽有前景但尚未定论。因此，我们进一步讨论了OT在临床有效应用中的几个生理和方法学限制，以及如何通过应用合成OT受体（OTR）激动剂来缓解这些限制。最后，我们讨论了前沿药理学和基因疗法的潜在疗效，这些疗法旨在特异性增强内源性OT释放，从而挽救重度AUD和其他不治之症患者大脑中OT的表达缺陷。
