Regulation of CRE-mediated transcription in mouse brain by amphetamine

Tamara Z. Shaw-Lutchman, Soren Impey, Daniel Storm, Eric J. Nestler

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Previous work has demonstrated that acute and chronic administration of amphetamine causes phosphorylation of the transcription factor CREB, the cAMP response element (CRE) binding protein, in striatum, a brain region important for the behavioral actions of the drug. To determine whether such phosphorylation is associated with changes in CREB transcriptional activity, we mapped β-galactosidase (β-gal) expression in a CRE-LacZ transgenic mouse, in which the β-gal reporter is downstream of CRE sequences, following acute or chronic amphetamine administration. We found that acute amphetamine induced β-gal expression in a relatively small number of brain regions, including nucleus accumbens (ventral striatum), amygdala, ventral tegmental area, and locus coeruleus. Chronic amphetamine generally produced greater changes in CRE-mediated transcription in most brain regions and induced CRE-transcription in several regions unaffected by acute drug exposure. Interestingly, amphetamine regulation of CRE activity differed dramatically between males and females. In nucleus accumbens, β-gal expression colocalized predominantly with dynorphinergic neurons after acute amphetamine administration, while chronic administration induced β-gal expression in both dynorphinergic and enkephalinergic neurons. In ventral tegmental area, acute and chronic amphetamine induced β-gal expression mainly in dopaminergic neurons, while induction in the locus coeruleus occurred mainly in nonnoradrenergic neurons. This study identifies several brain regions where CRE-mediated transcription may play a key role in the development of neuronal plasticity associated with amphetamine administration.

Original languageEnglish (US)
Pages (from-to)10-17
Number of pages8
JournalSynapse
Volume48
Issue number1
DOIs
StatePublished - Apr 1 2003

Keywords

  • Addiction
  • Amygdala
  • CREB
  • Gene expression
  • Locus coeruleus
  • Nucleus accumbens
  • Ventral tegmental area

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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