Monosodium glutamate, a food additive, induces depressive-like and anxiogenic-like behaviors in young rats

Life Sci. 2014 Jun 27;107(1-2):27-31. doi: 10.1016/j.lfs.2014.04.032. Epub 2014 May 5.


Monosodium glutamate (MSG) has been the target of research due to its toxicological effects.

Aims: We investigated the depressive- and anxiogenic-like behaviors in rats exposed to neonatal subcutaneous injection of MSG. The involvement of the serotonergic system, by measuring [(3)H] serotonin (5-HT) uptake in cerebral cortices, and the hypothalamic pituitary adrenal (HPA) axis, by determining serum adrenocorticotropic hormone (ACTH) and corticosterone levels, was also examined.

Materials and methods: Male and female newborn Wistar rats were divided into control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4 g/kg/day) from the 1st to 5th postnatal day. The behavioral tests [spontaneous locomotor activity, contextual fear conditioning, and forced swimming test (FST)] were performed from the 60th to 64th postnatal day. MSG-treated animals showed alteration in the spontaneous locomotor activity, an increase in the number of fecal pellets and the number of animal's vocalizations and urine occurrence, and a decrease in the grooming time.

Key findings: The MSG exposure increased the immobility time in the FST and the freezing reaction in the contextual fear conditioning. Additionally, MSG treatment increased the [(3)H]5-HT uptake in the cerebral cortices of rats and induced a deregulation of HPA axis function (by increasing serum ACTH and corticosterone levels).

Significance: In conclusion MSG-treated rats are more susceptible to develop anxiogenic- and depressive-like behaviors, which could be related to a dysfunction in the serotonergic system.

Keywords: Anxiogenic-like behavior; Depressive-like behavior; HPA axis; Monosodium glutamate; Serotonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Animals, Newborn
  • Anxiety Disorders / chemically induced*
  • Anxiety Disorders / metabolism
  • Behavior, Animal / drug effects*
  • Cerebral Cortex / drug effects
  • Corticosterone / metabolism
  • Depressive Disorder / chemically induced*
  • Depressive Disorder / metabolism
  • Fear / drug effects
  • Female
  • Flavoring Agents / toxicity*
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Injections, Subcutaneous
  • Locomotion / drug effects
  • Male
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Radioimmunoassay
  • Rats
  • Rats, Wistar
  • Serotonin / metabolism
  • Sodium Glutamate / toxicity*
  • Swimming / physiology


  • Flavoring Agents
  • Serotonin
  • Adrenocorticotropic Hormone
  • Sodium Glutamate
  • Corticosterone