Phosphodiesterase (PDE) inhibitors are a class of anti-inflammatory drugs that decrease ethanol drinking (for further review, see (Logrip, 2015; Wen et al., 2018)). Preclinical work examining the effects of PDE inhibitors on ethanol-related behaviors is summarized in Table 3. PDEs regulate several intracellular signaling cascades by reducing cAMP and cGMP levels, which may contribute to excessive ethanol intake (Logrip, 2015). Ibudilast, a non-specific PDE inhibitor, decreases ethanol consumption in rodent models (Bell et al., 2013). There are several isoforms of PDE comprising 11 different families based on structure and functional specificity. PDE-10 inhibition also reduces ethanol self-administration in rats (Logrip et al., 2014). Furthermore, specific PDE-4 inhibitors reduce ethanol consumption. By increasing cAMP levels, PDE-4 inhibitors exhibit a general anti-inflammatory effect in a variety of inflammatory conditions (Zebda and Paller, 2018). Hu et al. (2011) found that treatment with specific PDE-4 inhibitors, rolipram or Ro 20–1724, reduces ethanol intake and preference in mice. Rolipram also decreases ethanol consumption in Fawn-Hooded rats (Wen et al., 2012). Another study testing nine PDE inhibitors with different subtype selectivity shows that only the PDE-4
