The potent free radical scavenger alpha-lipoic acid improves memory in aged mice: putative relationship to NMDA receptor deficits

Pharmacol Biochem Behav. 1993 Dec;46(4):799-805. doi: 10.1016/0091-3057(93)90204-7.


alpha-Lipoic acid (alpha-LA) improved longer-term memory of aged female NMRI mice in the habituation in the open field test at a dose of 100 mg/kg body weight for 15 days. In a separate experiment, no such effect could be found for young mice. alpha-LA alleviated age-related NMDA receptor deficits (Bmax) without changing muscarinic, benzodiazepine, and alpha 2-adrenergic receptor deficits in aged mice. The carbachol-stimulated accumulation of inositol monophosphates was not changed by the treatment with alpha-LA. These results give tentative support to the hypothesis that alpha-LA improves memory in aged mice, probably by a partial compensation of NMDA receptor deficits. Possible modes of action of alpha-LA based on its free radical scavenger properties are discussed in relation to the membrane hypothesis of aging.

MeSH terms

  • Aging / psychology*
  • Animals
  • Behavior, Animal / drug effects
  • Brain Chemistry / drug effects
  • Carbachol / pharmacology
  • Cognition / drug effects
  • Dizocilpine Maleate / pharmacology
  • Female
  • Free Radical Scavengers*
  • Habituation, Psychophysiologic
  • Inositol Phosphates / metabolism
  • Memory / drug effects*
  • Mice
  • Receptors, Adrenergic / drug effects
  • Receptors, Adrenergic, alpha-2 / drug effects
  • Receptors, GABA-A / drug effects
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Thioctic Acid / pharmacology*


  • Free Radical Scavengers
  • Inositol Phosphates
  • Receptors, Adrenergic
  • Receptors, Adrenergic, alpha-2
  • Receptors, GABA-A
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • Thioctic Acid
  • Carbachol