The levo enantiomer of amphetamine increases memory consolidation and gene expression in the hippocampus without producing locomotor stimulation.

Full Abstract

Dextro-amphetamine enhances memory and other cognitive functions in animals and humans. The use of d-amphetamine as a memory enhancer, however, is limited by a robust stimulatory side-effect profile caused by release of dopamine. The levo enantiomer of amphetamine has been shown to be considerably less effective as a dopamine releaser and less potent in producing the stimulatory effects characteristic of d-amphetamine. In order to determine whether l-amphetamine and the structurally related compound, l-methamphetamine, retain cognitive-enhancing effects despite their lack of stimulatory activity, we administered the compounds to rats prior to activity monitoring experiments, and in different animals, immediately after training on inhibitory avoidance and object recognition tasks. Results demonstrated that l-amphetamine and l-methamphetamine did not increase locomotion and stereotypies beyond control levels, but did produce significant memory enhancement. In addition, l-amphetamine and l-methamphetamine alleviated scopolamine-induced amnesia in the inhibitory avoidance task. In all cases, these compounds produced an effect comparable to that of d-amphetamine, but required only one quarter of the d-amphetamine dose to produce the same effect size. We also found that l-amphetamine modulates learning-induced changes in hippocampal Arc/Arg3.1 protein synthesis that correlate with memory consolidation. These results suggest that l-amphetamine and l-methamphetamine are potent memory enhancers in rats and may ultimately be useful for treating memory disorders in humans.

Author information

Author/s: Wiig, Kjesten A (KA); Whitlock, Jonathan R (JR); Epstein, Mel H (MH); Carpenter, Randall L (RL); Bear, Mark F (MF);

Affiliation: Sention Inc, Providence, RI 02906, USA.

Journal and publication information

Publication Type: Journal Article

Journal: Neurobiology of learning and memory (Neurobiol Learn Mem), published in United States. (Language: eng)

Reference: 2009-Jul; vol 92 (issue 1) : pp 106-13

Dates: Created 2009/05/12; Completed 2009/08/17;

PMID: 19368765, status: MEDLINE (last retrieval date: 8/21/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Amnesia - chemically induced; drug therapy
Amphetamine - administration & dosage
Animals
Avoidance Learning - drug effects
Central Nervous System Stimulants - administration & dosage
Cytoskeletal Proteins - genetics; metabolism
Dextroamphetamine - administration & dosage
Gene Expression - drug effects
Hippocampus - drug effects; metabolism

Male
Memory - drug effects
Methamphetamine - administration & dosage
Motor Activity - drug effects
Nerve Tissue Proteins - genetics; metabolism
Rats
Rats, Long-Evans
Recognition (Psychology) - drug effects
Scopolamine

Associated Chemicals: Central Nervous System Stimulants (0) ; Cytoskeletal Proteins (0) ; Nerve Tissue Proteins (0) ; activity regulated cytoskeletal-associated protein (0) ; Amphetamine (300-62-9) ; Scopolamine (51-34-3) ; Dextroamphetamine (51-64-9) ; Methamphetamine (537-46-2)

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