Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and interaction and repetitive behaviors. A chromosome 15q11-13 paternal duplication (15q dup) mouse corresponding to the most cytogenetically frequent CNV in ASD have core symptoms of ASD-like behaviors. Recently, we found that 15q dup mice showed a hyposerotonergic state in the brain and a reduction in the neuronal activity of the dorsal raphe nucleus (DRN) neurons. Also, we found that administration of the SSRI fluoxetine during the early postnatal period normalized the serotonin (5-HT) contents in adulthood. Together with the serotonin restoration, impairments of electrophysiological properties in the DRN and a social behavior were ameliorated. 5-HT is a well-known modulator of behavioral, physiological, and emotional functions at forebrain region. In this study, we investigated the relationship between the sociability and the magnitude of 5-HT_1A receptor (5-HT_1AR) activation-induced outward currents from layer V pyramidal neurons in the prefrontal cortex (PFC), because a mouse model of Williams-Beuren syndrome, another developmental disorder exhibiting low innate anxiety and high sociability, reportedly showed larger 5-HT-induced currents. Using whole cell recording from layer V neurons in acute adult brain slices of PFC (～3 month-aged), we found 5-HT elicited significantly larger outward currents in 15q dup mice than in WT controls. In contrast, baclofen-induced GABA_B receptor-mediated outward currents were not significantly different between genotypes, although GABA_B receptor was also coupled to G_i/o as well as 5-HT_1AR. As for excitatory/inhibitory (E/I), we found the E/I balance at the PFC layer V neurons shifted toward the excitatory in 15q dup mice, consistent with our previous study observed in the sensory cortex. Further, the imbalance of E/I ratio lowered the threshold for inducing synaptic plasticity. The present results suggest that increased modulatory effect of 5-HT_1ARs is observed through the several developmental disorders with impairment of sociability or anxiety and compensates the imbalance of the neuronal circuity in the PFC.