Neurobehavioral and biochemical effects of magnesium chloride (MgCl2), magnesium sulphate (MgSO4) and magnesium-L-threonate (MgT) supplementation in rats: A dose dependent comparative study

Pak J Pharm Sci. 2019 Jan;32(1(Supplementary)):277-283.


Magnesium (Mg) is an essential biomineral that acts as an intracellular cofactor for more than 300 enzymes. It is an important modulator of the N-methyl-D-aspartate (NMDA) receptor which is involved in memory function and depression. The purpose of this study was to compare the dose dependent effect of oral supplementation of Magnesium chloride (MgCl2), Magnesium sulphate (MgSO4) and Magnesium-L-threonate (MgT) on memory and depression-related behaviors in rats. Rats were orally administered with different doses (50 mg/kg, 100 mg/kg and 150 mg/kg) of each Mg salt. Following 28 days of oral supplementation, animals were subjected to behavioral tests. After completion of behavioral test, rats were decapitated. Brain and plasma samples were used for neurochemical and biochemical analysis. Assessment of behaviors in elevated plus maze (EPM) test and forced swim test (FST) showed that MgT more significantly improved memory of rats and decreased depression-like symptoms in healthy rats as compared to controls. Biochemical analysis indicated significant increase in plasma Mg levels dose dependently following MgT administration. This increase might be related to observe enhanced cholinergic functions and decline in oxidative stress in rats in the present study. This comparative study highlights that MgT (100mg/kg) is the most appropriate Mg salt and dose for oral treatment that strengthens cholinergic system and improves brain related functions through attenuation of oxidative burden in adult healthy rats.

Publication types

  • Comparative Study

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Butyrates / administration & dosage
  • Butyrates / pharmacology*
  • Depression / drug therapy
  • Dose-Response Relationship, Drug
  • Magnesium / blood
  • Magnesium Chloride / administration & dosage
  • Magnesium Chloride / pharmacology*
  • Magnesium Sulfate / administration & dosage
  • Magnesium Sulfate / pharmacology*
  • Male
  • Memory / drug effects*
  • Rats, Wistar


  • Butyrates
  • Magnesium Chloride
  • Magnesium Sulfate
  • Magnesium
  • Acetylcholine
  • threonic acid