The potent free radical scavenger alpha-lipoic acid improves memory in aged mice: putative relationship to NMDA receptor deficits.
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.
Stoll
S
S
Central Institute for Mental Health, Department of Psychopharmacology, Mannheim, Germany.
Hartmann
H
H
Cohen
S A
SA
Müller
W E
WE
D000375:Aging / Q000523:psychology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005260:Female; D016166:Free Radical Scavengers; D006185:Habituation, Psychophysiologic; D007295:Inositol Phosphates / Q000378:metabolism; D008568:Memory / Q000187:drug effects*; D051379:Mice; D011941:Receptors, Adrenergic / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D008063:Thioctic Acid / Q000494:pharmacology*
D016166:Free Radical Scavengers; D007295:Inositol Phosphates; D011941:Receptors, Adrenergic; D018341:Receptors, Adrenergic, alpha-2; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008063:Thioctic Acid; D002217:Carbachol