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Psychopharmacology

, Volume 235, Issue 8, pp 2377–2385 | Cite as

Inhibition of phosphodiesterase 2 by Bay 60-7550 decreases ethanol intake and preference in mice

  • Jing Shi
  • Huaxia Liu
  • Jianchun Pan
  • Jie Chen
  • Nianping Zhang
  • Kaiping Liu
  • Ning Fei
  • James M. O’Donnell
  • Han-Ting Zhang
  • Ying Xu
Original Investigation

Abstract

Rationale

Alcohol use disorder (AUD) is a chronically relapsing condition, which affects nearly 11% of population worldwide. Currently, there are only three FDA-approved medications for treatment of AUD, and normally, satisfactory effects are hard to be achieved. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling has been implicated in regulation of ethanol intake. Phosphodiesterase 2 (PDE), a dual substrate PDE that hydrolyzes both cAMP and cGMP, may play a crucial role in regulating ethanol consumption.

Methods

The present study determined whether PDE2 was involved in the regulation of ethanol intake and preference. The two-bottle choice procedure was used to examine the effects of the selective PDE2 inhibitor Bay 60-7550 on ethanol intake. The sucrose and quinine intake (taste preference) and locomotor activity (sedative effects) were also measured to exclude the false positive effects of Bay 60-7550.

Results

Treatment with Bay 60-7550 (1 and 3 mg/kg, i.p.) decreased ethanol intake and preference, without changing total fluid intake. In addition, Bay 60-7550 at doses that reduced ethanol intake did not affect sucrose and quinine intake and preference, which excluded the potential influence of taste preference and sedative effects on ethanol drinking behavior. Moreover, Bay 60-7550 at 3 mg/kg did not alter locomotor activity or ethanol metabolism, further supporting the specific effect of Bay 60-7550 on ethanol drinking behavior.

Conclusions

The results suggest that PDE2 plays a role in the regulation of ethanol consumption and that PDE2 inhibitors may be a novel class of drugs for treatment of alcoholism.

Keywords

PDE2 Bay 60-7550 cAMP/cGMP Ethanol intake Two-bottle choice 

Notes

Acknowledgements

This work was supported by research grants from NIH/NIAAA (HHSN275201700001C to H.-T. Zhang), National Nature Science Foundation of China (81773717 to H.-T. Zhang), and the Foundation of Overseas Distinguished Taishan Scholars of Shandong Province, China (to H.-T. Zhang). This work was also supported by The “13th Five-Year” Chinese Medicine Key Discipline in Zhejiang Province-Chinese Medicine Quality and functional evaluation (2017-XK-A43 to J. Shi).

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Copyright information

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

Authors and Affiliations

  • Jing Shi
    • 1
  • Huaxia Liu
    • 2
  • Jianchun Pan
    • 3
  • Jie Chen
    • 3
  • Nianping Zhang
    • 4
  • Kaiping Liu
    • 3
  • Ning Fei
    • 3
  • James M. O’Donnell
    • 5
  • Han-Ting Zhang
    • 6
    • 7
  • Ying Xu
    • 5
  1. 1.School of PharmacyHangzhou Medical CollegeHangzhouChina
  2. 2.School of NursingTaishan Medical UniversityTai’anChina
  3. 3.Brain InstituteWenzhou Medical University School of PharmacyWenzhouChina
  4. 4.Datong University Medical CollegeDatongChina
  5. 5.Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical SciencesUniversity at Buffalo, the State University of New YorkBuffaloUSA
  6. 6.Departments of Behavioral Medicine & Psychiatry and Physiology, Pharmacology & Neuroscience, Rockefeller Neurosciences InstituteWest Virginia University Health Sciences CenterMorgantownUSA
  7. 7.Institute of PharmacologyTaishan Medical UniversityTai’anChina

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