Chronic inhibition of glutamine synthetase is not associated with impairment of learning and memory in mice

Brain Res Bull. 2002 Jan 1;57(1):11-5. doi: 10.1016/s0361-9230(01)00631-1.


The convulsant methionine sulfoximine (MSO) is a byproduct of the agenized flour commonly used for feeding domestic animals decades ago. MSO is a powerful glycogenic and epileptogenic agent, and it is an irreversible inhibitor of glutamine synthetase. This latter effect was hypothesized to be responsible for the increase in the incidence of some neuropathologies in humans, such as Alzheimer's disease or Parkinson's disease. In order to test this hypothesis, we chronically administered MSO to two inbred strains of mice, C57BL/6J and BALB/cJ, and analyzed possible alterations in learning and memory features of these mice. Mice were given 20 mg/kg of MSO three times a week for 10 weeks. Spatial learning capabilities assessed with a radial maze were not affected by the long-term MSO treatment, although activity was significantly decreased in BALB/cJ mice. Thus, our data suggest that long-term administration of non-convulsive and non-glycogenic doses of MSO do not alter the spatial memory of mice. Our results do not support the hypothesis that chronic treatment with MSO influences hippocampus-dependent learning abilities in mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / physiopathology
  • Brain Chemistry / drug effects*
  • Brain Chemistry / physiology
  • Glutamate-Ammonia Ligase / antagonists & inhibitors*
  • Glutamate-Ammonia Ligase / metabolism
  • Glutamic Acid / metabolism*
  • Learning Disabilities / chemically induced*
  • Learning Disabilities / metabolism
  • Learning Disabilities / physiopathology
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Memory Disorders / chemically induced*
  • Memory Disorders / metabolism
  • Memory Disorders / physiopathology
  • Methionine Sulfoximine / toxicity*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neurodegenerative Diseases / chemically induced*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Neurons / drug effects
  • Neurons / metabolism


  • Methionine Sulfoximine
  • Glutamic Acid
  • Glutamate-Ammonia Ligase