# The intake of monosodium aspartate attenuates aggression induced by post-weaning social isolation in an ADHD rat model

## TL;DR

Monosodium aspartate reduces aggression in ADHD rats through gut-brain communication, similar to monosodium glutamate.

## Contribution

MSA reduces aggression via the gut-brain axis, involving the iNTS and CeA, and is a safer alternative to MSG.

## Key findings

- MSA ingestion significantly reduces aggression frequency and duration in isolated ADHD rats.
- Vagotomy eliminates MSA's anti-aggressive effects and its impact on iNTS and CeA activation.
- MSA does not affect anxiety-like behavior in the open field test.

## Abstract

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.

•MSA reduces aggression in ADHD rat model via gut-brain interaction.•MSA activates iNTS and modulate CeA similarly to MSG, confirmed by c-Fos expression.•Vagotomy blocks iNTS activation, CeA modulation and MSA's anti-aggressive effects.•MSA does not alter anxiety-like behavior in open field test.•MSA may be a safer alternative to MSG for behavioral modulation.

MSA reduces aggression in ADHD rat model via gut-brain interaction.

MSA activates iNTS and modulate CeA similarly to MSG, confirmed by c-Fos expression.

Vagotomy blocks iNTS activation, CeA modulation and MSA's anti-aggressive effects.

MSA does not alter anxiety-like behavior in open field test.

MSA may be a safer alternative to MSG for behavioral modulation.