Regulation of CRE-mediated transcription in mouse brain by amphetamine

Synapse. 2003 Apr;48(1):10-7. doi: 10.1002/syn.10172.


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 beta-galactosidase (beta-gal) expression in a CRE-LacZ transgenic mouse, in which the beta-gal reporter is downstream of CRE sequences, following acute or chronic amphetamine administration. We found that acute amphetamine induced beta-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, beta-gal expression colocalized predominantly with dynorphinergic neurons after acute amphetamine administration, while chronic administration induced beta-gal expression in both dynorphinergic and enkephalinergic neurons. In ventral tegmental area, acute and chronic amphetamine induced beta-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphetamine / pharmacology*
  • Animals
  • Brain / drug effects*
  • Brain / metabolism
  • Central Nervous System Stimulants / pharmacology*
  • Cyclic AMP Response Element-Binding Protein / drug effects*
  • Female
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Mice
  • Mice, Transgenic
  • Sex Characteristics
  • Time Factors
  • beta-Galactosidase / biosynthesis*


  • Central Nervous System Stimulants
  • Cyclic AMP Response Element-Binding Protein
  • Amphetamine
  • beta-Galactosidase