This range of rolipram-induced behaviors likely reflects the importance of specific PDE4 subtypes in regulating distinct behaviors: genetic studies in mice have revealed that anxiety is largely regulated by PDE4A and PDE4B, psychosis by PDE4B, and depression and cognition by PDE4D (Hansen et al., 2014, Li et al., 2011, Siuciak et al., 2007, Siuciak et al., 2008, Zhang et al., 2002, Zhang et al., 2008). Here, PDE4B is linked to major depressive disorder.