Lithium effects on brain glutamatergic and GABAergic systems of healthy volunteers as measured by proton magnetic resonance spectroscopy

Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jan 1;32(1):249-56. doi: 10.1016/j.pnpbp.2007.08.015. Epub 2007 Aug 22.


Lithium is a first-line medicinal treatment for acute bipolar disorder and is also used prophylactically in manic depressive illnesses; however, its mechanism of action is still largely unknown. Animal and human studies have suggested that lithium modulates glutamatergic and GABAergic neurotransmissions. The aim of this study is to investigate the effects of lithium on brain glutamate (Glu), glutamine (Gln), and gamma-aminobutyric acid (GABA) levels in healthy individuals using proton magnetic resonance spectroscopy (1H-MRS). In vivo 3 Tesla 1H-MRS was performed on the anterior cingulate cortex and bilateral basal ganglia initially and after two weeks of lithium administration on 8 healthy male subjects who had a mean age of 34.9 years. After two weeks of lithium administration, Gln significantly decreased in the left basal ganglia and showed a decreasing trend in the right basal ganglia. Additionally, Glu+Gln (Glx) significantly decreased in the right basal ganglia and showed a decreasing trend in the left basal ganglia. Glu did not significantly change in any of the three tested areas, and GABA exhibited no significant change after the lithium administration when measured in the anterior cingulate cortex and left basal ganglia. This study is the first to demonstrate that subchronic lithium treatment decreases Gln and Glx levels in the bilateral basal ganglia of healthy individuals. Our finding might suggest that the decrease of Glx levels is associated with the pharmacological actions of subchronic lithium treatment.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antimanic Agents / pharmacology*
  • Brain / drug effects*
  • Brain Mapping
  • Glutamic Acid / metabolism*
  • Humans
  • Lithium / pharmacology*
  • Magnetic Resonance Spectroscopy / methods*
  • Male
  • Middle Aged
  • Protons
  • gamma-Aminobutyric Acid / metabolism*


  • Antimanic Agents
  • Protons
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Lithium