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CAMKII-conditional deletion of histone deacetylase 2 potentiates acute methamphetamine-induced expression of immediate early genes in the mouse nucleus accumbens.
- Source :
-
Scientific reports [Sci Rep] 2015 Aug 24; Vol. 5, pp. 13396. Date of Electronic Publication: 2015 Aug 24. - Publication Year :
- 2015
-
Abstract
- Methamphetamine (METH) produces increases in the expression of immediate early genes (IEGs) and of histone deacetylase 2 (HDAC2) in the rat nucleus accumbens (NAc). Here, we tested whether HDAC2 deletion influenced the effects of METH on IEG expression in the NAc. Microarray analyses showed no baseline differences in IEG expression between wild-type (WT) and HDAC2 knockout (KO) mice. Quantitative-PCR analysis shows that an acute METH injection produced time-dependent increases in mRNA levels of several IEGs in both genotypes. Interestingly, HDAC2KO mice displayed greater METH-induced increases in Egr1 and Egr2 mRNA levels measured at one hour post-injection. The levels of Fosb, Fra2, Egr1, and Egr3 mRNAs stayed elevated in the HDAC2KO mice 2 hours after the METH injection whereas these mRNAs had normalized in the WT mice. In WT mice, METH caused increased HDAC2 recruitment to the promoters some IEGs at 2 hours post injection. METH-induced prolonged increases in Fosb, Fra2, Egr1, and Egr3 mRNA levels in HDAC2KO mice were associated with increased enrichment of phosphorylated CREB (pCREB) on the promoters of these genes. Based on our observations, we hypothesize that HDAC2 may regulate the expression of these genes, in part, by prolonging the actions of pCREB in the mouse NAc.
- Subjects :
- Animals
Cyclic AMP Response Element-Binding Protein metabolism
Histone Deacetylase 2 metabolism
Male
Mice, Knockout
Nucleus Accumbens drug effects
Phosphorylation drug effects
Promoter Regions, Genetic genetics
Protein Binding drug effects
RNA, Messenger genetics
RNA, Messenger metabolism
Time Factors
Transcription Factor AP-1 metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2 metabolism
Gene Deletion
Gene Expression Regulation drug effects
Genes, Immediate-Early
Histone Deacetylase 2 deficiency
Methamphetamine pharmacology
Nucleus Accumbens metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26300473
- Full Text :
- https://doi.org/10.1038/srep13396