Inhibition of phosphodiesterase 2 by Bay 60-7550 decreases ethanol
intake and preference in mice
James M. O’Donnell
Received: 20 April 2018 / Accepted: 24 May 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
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, satis-
factory 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,mayplayacrucialroleinregulatingethanol
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.
Jing Shi and Huaxia Liu contributed equally to this work.
Han-Ting Zhang and Ying Xu jointly directed this study.
* Han-Ting Zhang
* Ying Xu
School of Pharmacy, Hangzhou Medical College,
Hangzhou 310053, Zhejiang Province, China
School of Nursing, Taishan Medical University,
Tai ’an 271016, Shandong Province, China
Brain Institute, Wenzhou Medical University School of Pharmacy,
Wenzhou 325021, Zhejiang Province, China
Datong University Medical College, Datong 037009, Shanxi
Department of Pharmaceutical Sciences, School of Pharmacy and
Pharmaceutical Sciences, University at Buffalo, the State University
of New York, Buffalo, NY 14214, USA
Departments of Behavioral Medicine & Psychiatry and Physiology,
Pharmacology & Neuroscience, Rockefeller Neurosciences Institute,
West Virginia University Health Sciences Center,
Morgantown, WV 26506, USA
Institute of Pharmacology, Taishan Medical University,
Tai ’an 271016, Shandong, China