, Volume 235, Issue 6, pp 1793–1805 | Cite as

Cyclic nucleotide phosphodiesterases: potential therapeutic targets for alcohol use disorder

  • Rui-Ting Wen
  • Fang-Fang Zhang
  • Han-Ting Zhang


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.


Alcohol use disorder (AUD) Central nervous system Alcohol dependence cAMP cGMP Phosphodiesterase (PDE) 



This work was supported by the research grants from NIH/NIAAA (AA020042, HHSN275201700001C; both to H.-T. Zhang), the Foundation of Overseas Distinguished Taishan Scholars of Shandong Province, China (to H.-T. Zhang), and National Nature Science Foundation of China (81773717, 81503050, to H.-T. Zhang and R.-T. Wen, respectively).


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Rui-Ting Wen
    • 1
  • Fang-Fang Zhang
    • 2
  • Han-Ting Zhang
    • 2
    • 3
  1. 1.Department of PharmacyPeking University People’s HospitalBeijingChina
  2. 2.Institute of PharmacologyQilu Medical UniversityTaianChina
  3. 3.Departments of Behavioral Medicine and Psychiatry and Physiology, Pharmacology and Neuroscience, Rockefeller Neurosciences InstituteWest Virginia University Health Sciences CenterMorgantownUSA

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