Oral Ingestion of Umami during the Developmental Period Is Involved in Emotion Formation via the Vagus Nerve in Attention Deficit Hyperactivity Disorder Model Rats

Monosodium glutamate (MSG), an umami substance, activates the gut-brain axis via vagus nerves. However, the brain mechanism involved in the effect of MSG on aggression during the developmental period has not been clarified. SHR/Izm, a known model of attention-deficit hyperactivity disorder (ADHD), was used to investigate the effect of MSG oral ingestion (60 mM solution) on aggression. The resident-intruder test was performed in rats, with a detailed analysis of aggressive behavior, including the frequency, duration, and latency of anogenital sniffing, aggressive grooming, and attack behavior. Immunohistochemistry of c-Fos expression was then investigated in aggression-related brain areas such as the pre-frontal cortex (PFC), lateral hypothalamus (LH), and central amygdala (CeA). The resident intruder test conducted during the dark phase revealed that MSG ingestion significantly decreased the frequency and duration of aggressive grooming and attack behavior and increased the latency of attack behavior compared with the control group. The immunostaining of c-Fos revealed that MSG ingestion increased the number of positive cells in the intermediate nucleus of the solitary tract (iNTS), a terminal of the gastrointestinal sensory afferent fiber of the vagus nerve (p=0.0094), and decreased c-Fos expression in the CeA (p=0.0084). However, c-Fos expression in the PFC and LH was comparable between the MSG-treated and control groups. Data suggest that MSG ingestion decreased isolation-induced aggression in the rat model of ADHD, SHR/Izm, which was mediated by the vagus nerve related to c-Fos activation in the iNTS and c-Fos inactivation in the CeA.