title: Regulation of CRE-mediated transcription in mouse brain by amphetamine.
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 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.
authors.affiliation: Deparment of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9070, USA.
authors.forename: Tamara Z
authors.initials: TZ
authors.lastname: Shaw-Lutchman
authors.forename: Soren
authors.initials: S
authors.lastname: Impey
authors.forename: Daniel
authors.initials: D
authors.lastname: Storm
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Nestler
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects*; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012727:Sex Characteristics; D013997:Time Factors; D001616:beta-Galactosidase / Q000096:biosynthesis*
chemical_list: D000697:Central Nervous System Stimulants; D017362:Cyclic AMP Response Element-Binding Protein; D000661:Amphetamine; D001616:beta-Galactosidase