Monosodium glutamate-associated alterations in open field, anxiety-related and conditioned place preference behaviours in mice

Naunyn Schmiedebergs Arch Pharmacol. 2017 Jul;390(7):677-689. doi: 10.1007/s00210-017-1371-6. Epub 2017 Mar 29.


The present study investigated changes in behaviour associated with oral monosodium glutamate (a flavouring agent), using the open field, elevated plus maze and conditioned place preference (CPP) paradigms, respectively. Mice were assigned to two groups for CPP [monosodium glutamate (MSG)-naïve (n = 40) and MSG-pretreated (n = 40)] and two groups for open field (OF) and elevated plus maze (EPM) tests [n = 40 each], respectively. Animals in respective groups were then divided into four subgroups (n = 10) (vehicle or MSG (80, 160 and 320 mg/kg)). MSG-naïve mice were observed in the CPP box in three phases (pre-conditioning, conditioning and post-conditioning). Mice were conditioned to MSG or an equivalent volume of saline. The MSG pretreatment group received vehicle or respective doses of MSG daily for 21 days, prior to conditioning. Mice in the OF or EPM groups received vehicle or doses of MSG (orally) for 21 days, at 10 ml/kg. Open field or EPM behaviours were assessed on days 1 and 21. At the end of the experiments, mice in the OF groups were sacrificed and brain homogenates used to assay glutamate and glutamine. Results showed that administration of MSG was associated with a decrease in rearing, dose-related mixed horizontal locomotor, grooming and anxiety-related response and an increase in brain glutamate/glutamine levels. Following exposure to the CPP paradigm, MSG-naïve and MSG-pretreated mice both showed 'drug-paired' chamber preference. The study concluded that MSG (at the administered doses) was associated with changes in open field activities, anxiety-related behaviours and brain glutamate/glutamine levels; its ingestion also probably leads to a stimulation of the brain reward system.

Keywords: Conditioned place preference; Flavour enhancer; Glutamate; Novelty-induced behaviour.

MeSH terms

  • Animals
  • Anxiety / psychology*
  • Brain / drug effects
  • Brain / metabolism
  • Choice Behavior / drug effects*
  • Conditioning, Psychological / drug effects*
  • Glutamic Acid / analysis
  • Glutamine / analysis
  • Grooming / drug effects
  • Male
  • Maze Learning / drug effects
  • Mice
  • Motor Activity / drug effects*
  • Sodium Glutamate / pharmacology*


  • Glutamine
  • Glutamic Acid
  • Sodium Glutamate