Dopamine plays a central role in the regulation of psychomotor functions. The effect of dopamine is largely mediated through the cAMP/PKA signaling cascade and therefore controlled by phosphodiesterases (PDEs). Multiple PDEs with different substrate specificities and subcellular localization are expressed in the striatum, and the functional roles of PDE10A, PDE4, and PDE1B are extensively studied. Biochemical and behavioral profiles of PDE inhibition by selective inhibitors and/or genetic deletion related to dopaminergic neurotransmission are compared among those PDEs. The inhibition of PDE up-regulates cAMP/PKA signaling in three neuronal subtypes, resulting in the stimulation of dopamine synthesis at dopaminergic terminals, the inhibition of dopamine D₂–receptor signaling in striatopallidal neurons, and the stimulation of dopamine D₁–receptor signaling in striatonigral neurons. Predominant roles of PDE families or isoforms are implicated in each neuronal subtype: PDE4 at dopaminergic terminals, PDE10A and PDE4 in striatopallidal neurons, and PDE1B in striatonigral neurons. PDE10A and PDE4 inhibition may exhibit D₂ antagonist–like, antipsychotic effects, whereas PDE1B inhibition may exhibit D₁ agonist–like effects in the striatum. Development of PDE isoform–specific inhibitors is essential for better understanding of the function of each PDE isoform and treatment of neuropsychiatric disorders.