Department of Pharmacy, Peking University People's Hospital, Beijing, 100044, China.
Institute of Pharmacology, Qilu Medical University, Taian, 271016, Shandong, China.
Psychopharmacology (Berl). 2018 Jun;235(6):1793-1805. doi: 10.1007/s00213-018-4895-7. Epub 2018 Apr 16.
Alcohol use disorder (AUD), which combines the criteria of both alcohol abuse and dependence, contributes as an important causal factor to multiple health and social problems. Given the limitation of current treatments, novel medications for AUD are needed to better control alcohol consumption and maintain abstinence. It has been well established that the intracellular signal transduction mediated by the second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP) crucially underlies the genetic predisposition, rewarding properties, relapsing features, and systemic toxicity of compulsive alcohol consumption. On this basis, the upstream modulators phosphodiesterases (PDEs), which critically control intracellular levels of cyclic nucleotides by catalyzing their degradation, are proposed to play a role in modulating alcohol abuse and dependent process. Here, we highlight existing evidence that correlates cAMP and cGMP signal cascades with the regulation of alcohol-drinking behavior and discuss the possibility that PDEs may become a novel class of therapeutic targets for AUD.
酒精使用障碍（AUD），结合了酒精滥用和依赖的标准，是导致多种健康和社会问题的重要原因。鉴于目前治疗方法的局限性，需要新型的 AUD 药物来更好地控制饮酒量并保持戒断。已经充分证实，第二信使环腺苷酸（cAMP）和环鸟苷酸（cGMP）介导的细胞内信号转导对于强迫性饮酒的遗传易感性、奖励特性、复发特征和全身毒性至关重要。在此基础上，磷酸二酯酶（PDEs）作为上游调节剂，通过催化其降解来严格控制细胞内环核苷酸的水平，被认为在调节酒精滥用和依赖过程中发挥作用。在这里，我们强调了将 cAMP 和 cGMP 信号级联与调节饮酒行为相关的现有证据，并讨论了 PDE 可能成为 AUD 的一类新的治疗靶点的可能性。
