Effect of Novel Phosphodiesterase 4 (PDE4) Inhibitors on Ethanol Consumption in Mice

Nikoli Peacher* and Han-Ting Zhang, Department of Neuroscience, West Virginia University, Morgantown, WV 26506

Field (Broad Category): Neuroscience (Health Sciences) 

Student’s Major: Neuroscience 

Alcohol is one of the most widely used substances worldwide. Eighty-six percent of people 18 years old or older surveyed have consumed alcohol at some point in their lifetime. Alcohol use disorder is a psychiatric disorder that is characterized by a change in neuronal structure and function. Despite its prevalence, there are no ideal treatments. The cyclic adenosine monophosphate (cAMP) signaling pathway has been indicated as an important mediator in the development and maintenance of substance use disorders, including alcohol dependence. Novel drug therapies are targeted at the enzyme superfamily of phosphodiesterases (PDEs), specifically phosphodiesterase 4 (PDE4) which hydrolyzes cAMP and is found throughout the central nervous system. PDE4 inhibitors blocks the hydrolysis of cAMP and subsequently increase the levels of cAMP in the cells. The aim of the present study was to investigate the role of PDE4 inhibitors as a novel drug therapy for the treatment of alcohol dependence, through ethanol intake experiments. We hypothesize that the novel treatment with the ability to inhibit PDE4 will decrease ethanol consumption. To test the hypothesis, we will examine the effect of novel compounds, which have been shown to inhibit PDE4 in vitro, on ethanol intake and preference using ethanol two-bottle choice voluntary drinking in mice. If this is successful, we will discover PDE4 inhibitors for potential treatment of alcohol use disorders (this work was supported by the research grant from NIH/NIAAA HHS 75N94019C00010). 

Funding: NIH/NIAAA HHS 

Program/mechanism supporting research/creative efforts: WVU's Research Apprenticeship Program (RAP) & accompanying HONR 297-level course