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Mouse brain gene expression changes after acute and chronic amphetamine.

Boris P Sokolov1, Oxana O Polesskaya, George R Uhl

  • 1Molecular Neurobiology Branch, NIDA-IRP, NIH, Baltimore, Maryland, USA.

Journal of Neurochemistry
|February 1, 2003
PubMed
Summary
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Repeated amphetamine exposure alters gene expression in mouse brains, potentially explaining long-term psychostimulant effects. These changes, particularly in the frontal cortex, may underlie brain adaptations to drug use.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Long-term consequences of psychostimulant use may involve gene expression changes.
  • Understanding these molecular adaptations is crucial for addressing psychostimulant-related neurological effects.

Purpose of the Study:

  • To investigate gene expression alterations in mouse brains following acute and repeated amphetamine administration.
  • To identify candidate genes involved in brain adaptations to psychostimulants.

Main Methods:

  • Microarray analysis was used to examine the expression of 6340 genes in mouse brains.
  • Mice were treated with saline or amphetamine (single or repeated doses).
  • Gene expression changes were analyzed in whole brains, cerebral cortex, and brainstem.

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Main Results:

  • 117 transcripts showed drug-related expression changes (>1.8-fold difference) in response to amphetamine.
  • Acute amphetamine (SA) primarily enhanced expression, while repeated amphetamine (AA) reduced it.
  • Changes were more pronounced in the frontal cortex, and about a quarter persisted 20 hours post-injection.

Conclusions:

  • Gene expression modifications are implicated in the long-term effects of psychostimulant exposure.
  • Identified genes, including transcription factors and regulatory elements, are candidates for mediating brain adaptations to amphetamine.
  • These findings provide molecular insights into the neurobiological consequences of psychostimulant use.