Brain transcription factor expression: effects of acute and chronic amphetamine and injection stress

Antonio M. Persico, Charles W. Schindler, Bruce F. O'Hara, Michael T. Brannock, George R. Uhl

Research output: Contribution to journalArticle

Abstract

Amphetamine influences behaviors and the expression of transcription factor genes in the central nervous system (CNS). A single d-amphetamine dose (7.5 mg/kg, i.p.) enhances behavioral sterotypy and augments brain expression of c-fos, fos-B, fra-1, zif 268, jun-B, and c-jun by 2-11 fold. When the single amphetamine dose is preceeded by 28 saline injections over 14 days, it is half as effective in enhancing expression of these genes. Rats injected with 7.5 mg/kg i.p. twice daily for 2 weeks and sacrificed after the last injection reveal further attenuation or abolition of the amphetamine-induced mRNA upregulation. These stigmata of 'tolerance' in gene expression display partial overlap with behavioral tolerance, manifest as changes in locomotor activity. Rats receiving low (2 mg/kg) amphetamine challenge doses following the 2-week 7.5 mg/kg b.i.d. amphetamine treatment show tolerance to the locomotor activating effects of the drug; no tolerance is evident following a high (7.5 mg/kg) challenge dose. These data suggest that amphetamine-induced alterations in brain transcription factor gene expression can display 'tolerance' and possibly 'cross-tolerance' with the stress caused by i.p. injection.

Original languageEnglish (US)
Pages (from-to)91-100
Number of pages10
JournalMolecular Brain Research
Volume20
Issue number1-2
DOIs
StatePublished - 1993

Keywords

  • Amphetamine
  • C-fos
  • Immediate-early gene
  • Sensitization
  • Stress
  • Tolerance
  • Transcription factor

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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