PDE4A and depressive disorder: For example, in rodent models of depression, PDE4 inhibitors such as rolipram produce antidepressant-like effects comparable to selective serotonin reuptake inhibitors (SSRIs), driven by enhanced cAMP signaling and subsequent upregulation of CREB-mediated transcription of neurotrophic factors (Cong et al., 2023; Wachtel and Schneider, 1986; Zhang et al., 2017).