Some anti-inflammatory medications reduce alcohol consumption in rodent models. Inhibition of phosphodiesterases (PDE) increases cAMP and reduces inflammatory signaling. Rolipram, an inhibitor of PDE4, markedly reduced ethanol intake and preference in mice and reduced ethanol seeking and consumption in alcohol-preferring fawn-hooded rats (Hu et al., 2011; Wen et al., 2012). To determine if these effects were specific for PDE4, we compared nine PDE inhibitors with different subtype selectivity: propentofylline (nonspecific), vinpocetine (PDE1), olprinone, milrinone (PDE3), zaprinast (PDE5), rolipram, mesopram, piclamilast, and CDP840 (PDE4). Alcohol intake was measured in C57BL/6J male mice using 24-h two-bottle choice and two-bottle choice with limited (3-h) access to alcohol. Only the selective PDE4 inhibitors reduced ethanol intake and preference in the 24-h two-bottle choice test. For rolipram, piclamilast, and CDP840, this effect was observed after the first 6 h but not after the next 18 h. Mesopram, however, produced a long-lasting reduction of ethanol intake and preference. In the limited access test, rolipram, piclamilast, and mesopram reduced ethanol consumption and total fluid intake and did not change preference for ethanol, whereas CDP840 reduced both consumption and preference without altering total fluid intake. Our results provide novel evidence for a selective role of PDE4 in regulating ethanol drinking in mice. We suggest that inhibition of PDE4 may be an unexplored target for medication development to reduce excessive alcohol consumption.
Keywords: alcohol, two-bottle choice, PDE inhibitors, rolipram, mesopram, piclamilast, CDP840
Citation: Blednov YA, Benavidez JM, Black M and Harris RA (2014) Inhibition of phosphodiesterase 4 reduces ethanol intake and preference in C57BL/6J mice. Front. Neurosci. 8:129. doi: 10.3389/fnins.2014.00129
Received: 14 March 2014; Accepted: 08 May 2014;
Published online: 27 May 2014.
Edited by:Richard Lowell Bell, Indiana University School of Medicine, USA
Reviewed by:Asha Suryanarayanan, Manchester College School of Pharmacy, USA
Copyright © 2014 Blednov, Benavidez, Black and Harris. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: R. Adron Harris, Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA e-mail: firstname.lastname@example.org