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 language | English (US) |
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Pages (from-to) | 10-17 |
Number of pages | 8 |
Journal | Synapse |
Volume | 48 |
Issue number | 1 |
DOIs | |
State | Published - Apr 1 2003 |
Externally published | Yes |
Keywords
- Addiction
- Amygdala
- CREB
- Gene expression
- Locus coeruleus
- Nucleus accumbens
- Ventral tegmental area
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience