主催: 公益社団法人日本薬理学会
会議名: 第96回日本薬理学会年会
回次: 96
開催地: 横浜
開催日: 2022/11/30 - 2022/12/03
Individuals with autism spectrum disorders (ASDs) show neurobehavioral deficits, characterized by impairments in social interactions, repetitive behaviors, as well as wide sensory abnormalities. We have previously demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 (E12.5) causes autism-like behavioral abnormalities in male mouse offspring. We have also found that prenatal VPA exposure causes long-lasting mechanical allodynia and spinal microglial activation. In the present study, we aimed to investigate the role of the transient receptor potential vanilloid type 1 (TRPV1), a highly validated pain target, in abnormal pain sensitivity and social interaction deficits in prenatal VPA-treated mice. Behavioral analyses revealed that prenatal VPA-treated mice exhibited thermal hyperalgesia, mechanical allodynia and increased capsaicin-induced paw licking. A single administration of AMG517, a TRPV1 antagonist, alleviated both hyperalgesia and mechanical allodynia. Additionally, AMG517 reversed deficits in social behaviors in prenatal VPA-treated mice and also increased c-Fos expression, a marker for neuronal activity, in the nucleus accumbens. These findings suggest that prenatal exposure to VPA might alter TRPV1-mediated signaling and TRPV1 antagonists have a potential to treat certain cases of ASDs.