Abstract
Dysfunctions in the GABAergic system are associated with the pathogenesis of autism spectrum disorder (ASD). However, the mechanisms by which GABAergic system dysfunctions induce the pathophysiology of ASD remain unclear. We previously demonstrated that a selective type I 5α-reductase inhibitor SKF105111 (SKF) induced ASD-like behaviors, such as impaired sociability-related performance and repetitive grooming behaviors, in male mice. Moreover, the effects of SKF were caused by a decrease in the endogenous levels of allopregnanolone (ALLO), a positive allosteric modulator of the GABAA receptor. In this study, we used SKF-treated male mice as a putative animal model of ASD and examined the effects of Kami-shoyo-san (KSS) as an experimental therapeutic strategy for ASD. KSS is a traditional Kampo formula consisting of 10 different crude drugs and has been used for the treatment of neuropsychiatric symptoms. KSS dose-dependently attenuated sociability deficits and suppressed an increase in grooming behaviors in SKF-treated mice without affecting ALLO content in the prefrontal cortex. The systemic administration of the dopamine D1 receptor antagonist SCH23390 reversed the ameliorative effects of KSS. On the other hand, the dopamine D2 receptor antagonist sulpiride and GABAA receptor antagonist bicuculline only attenuated the ameliorative effect of KSS on repetitive self-grooming behaviors. The present results indicate that KSS improves SKF-induced ASD-like behaviors by facilitating dopamine receptor-mediated mechanisms and partly by neurosteroid-independent GABAA receptor-mediated neurotransmission. Therefore, KSS is a potential candidate for the treatment of ASD.
Highlights
We previously demonstrated that social isolation rearing in the early post-weaning period resulted in a number of behavioral abnormalities in male mice, such as increased spontaneous physical activity, learning and memory deficits, attention deficits, and social deficits [13,14,15,16], which are symptoms observed in developmental disorders including Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD)
We demonstrated that KSS improved ASD-like behaviors in SKF-treated male mice via the stimulation of dopaminergic and, partly, GABAA receptor mechanisms in the brain
Treatment of male mice with SKF, a type I 5α-reductase inhibitor, caused ASD-relevant behaviors such as impaired sociability-related performance and an increased level of repeated grooming behavior. These ASD-related behaviors exhibited by SKF-treated animals were consistent with our previous findings [19] showing that SKF downregulates brain ALLO biosynthesis and induces ASD-like behaviors in a manner that is reversible by exogenous ALLO and methylphenidate (MPH), a dopamine transporter inhibitor
Summary
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
