PDE4A and fragile X syndrome: Besides, pharmacological manipulation with agents that potentially increase cAMP, i.e., inhibitors of group II mGluRs and phosphodiesterase IV inhibitors (PDE4-Is), reversed the mGluR-LTD alteration in FXS mouse models (Choi et al., 2011, 2015, 2016), leading to the hypothesis that increasing cAMP formation might become a potential therapeutic strategy to rescue FXS phenotype.