Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by asynchronous development in several areas, such as communication, social behaviors, cognitive capabilities, and sensory responsiveness. The opioid system is well known to relieve pain and underpin the rewarding properties of most drugs of abuse. Additionally, accumulating evidence suggests that mu-opioid receptors (MORs) play an important role in modulating social behavior in humans and animals. We have investigated the effects of MOR agonists on social behavioral deficits in a mouse model of ASD and found that low to moderate MOR activation without analgesic efficacy ameliorated social impairments. Low doses of MOR agonists activated neurons in the medial prefrontal cortex and nucleus accumbens, while high doses caused a further increase in neural activity in the periaqueductal gray matter, a main site of the opioidergic analgesia. These results suggests that low-dose MOR agonists improve social behavioral deficits through activation of specific brain regions and might be useful for treating ASD symptoms. In this symposium, we would like to discuss about new treatment perspectives in ASD.