Yu Nishimura, Dewi Mustika, Shinya Ueno, Shiori Tominaga, Mariko Shindo, Naoki Tajiri, Cha-Gyun Jung, Hideki Hida
We investigated whether monosodium aspartate (MSA), an umami compound structurally analogous to monosodium glutamate (MSG), influences aggressive behavior in a rat model of attention-deficit/hyperactivity disorder. Spontaneously hypertensive rats (SHR/Izm) were subjected to post-weaning social isolation and assessed using the resident-intruder paradigm. MSA ingestion significantly reduced aggression, particularly the frequency and duration of attacks, while the open field test showed no differences in anxiety-like behavior. c-Fos immunohistochemistry revealed increased neuronal activation in the intermediate nucleus of the solitary tract (iNTS) and decreased activation in the central amygdala (CeA) following MSA ingestion. This effect, along with the reduction in aggression, was abolished by vagotomy, suggesting gut-brain involvement. These findings indicate that MSA, like MSG, can reduce aggression via the gut-brain axis, implicating the vagus nerve, iNTS and CeA as key mediators. This highlights that the modulation of aggression by ingested amino acids is a broader effect acting through shared mechanisms. © 2026 The Authors.
Department of Neurophysiology and Brain Science, Nagoya City University Graduate School of Medical Science, Mizuho-ku, Nagoya, 467-8601, Japan; Department of Physiology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia
