Neurodevelopmental disorder, attention deficit hyperactivity disorder (ADHD) is considered to affect the whole-brain, and one of candidate responsible brain region is the prefrontal cortex (PFC). The PFC regulates high-order cognitive functions, including attention, behavior and planning through working memory. As a medication for ADHD, α_2A-adrenergic receptor agonist, guanfacine (GFC) has been shown to improve PFC cognitive function, including working memory. However, it is poorly understood how GFC is effective in ADHD pathology in the PFC. In the present study, we first investigated the acute effects of GFC on ion channels that were proposed to be modulated by cAMP-PKA pathway in brain slice preparation of C57BL/6 mice. We used the somatic recording of patch-clamp techniques to record HCN channel- and KCNQ channel-mediated currents from layer 5 neurons of the PFC (2~3 month-aged). However, GFC did not show obvious modulatory effect on these current components. Next, we examined the modulatory effect of GFC on both EPSCs and IPSCs onto pyramidal neurons. For the recording of synaptic currents, recorded neurons were classified to two types (Callosal/Commissural (COM) and Corticopontine-projecting (CPn)). Although IPSCs were comparably inhibited in both types of neurons, EPSCs were suppressed in only COM-type neurons. These results may be able to explain a part of therapeutic mechanisms of GFC. In the future, it is necessary to clarify whether this target cell-dependent modulatory action is involved in the clinical effect of chronic administration of GFC.