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An Acute Methamphetamine Injection Downregulates the Expression of Several Histone Deacetylases (HDACs) in the Mouse Nucleus Accumbens: Potential Regulatory Role of HDAC2 Expression.
- Source :
-
Neurotoxicity research [Neurotox Res] 2016 Jul; Vol. 30 (1), pp. 32-40. Date of Electronic Publication: 2015 Dec 31. - Publication Year :
- 2016
-
Abstract
- Methamphetamine (METH) administration alters gene expression in the nucleus accumbens (NAc). We recently demonstrated that an acute METH injection produced prolonged increases in the expression of immediate early genes in the NAc of HDAC2-deficient mice, suggesting that HDAC2 might be an important regulator of gene expression in the rodent brain. Here, we tested the possibility that HDAC2 deletion might also impact METH-induced changes in the expression of various HDAC classes in the NAc. Wild-type (WT) and HDAC2 knockout (KO) mice were given a METH (20 mg/kg) injection, and NAc tissue was collected at 1, 2, and 8 h post treatment. We found that METH decreased HDAC3, HDAC4, HDAC7, HDAC8, and HDAC11 mRNA expression but increased HDAC6 mRNA levels in the NAc of WT mice. In contrast, the METH injection increased HDAC3, HDAC4, HDAC7, HDAC8, and HDAC11 mRNA levels in HDAC2KO mice. These observations suggest that METH may induce large-scale transcriptional changes in the NAc by regulating the expression of several HDACs, in part, via HDAC2-dependent mechanisms since some of the HDACs showed differential responses between the two genotypes. Our findings further implicate HDACs as potential novel therapeutic targets for neurotoxic complications associated with the abuse of certain psychostimulants.
- Subjects :
- Animals
Gene Expression Regulation, Enzymologic genetics
Histone Deacetylase 2 biosynthesis
Histone Deacetylase 2 genetics
Male
Mice
Mice, Knockout
Up-Regulation drug effects
Down-Regulation drug effects
Gene Expression Regulation, Enzymologic drug effects
Histone Deacetylase 2 physiology
Methamphetamine administration & dosage
Methamphetamine pharmacology
Nucleus Accumbens drug effects
Nucleus Accumbens metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1476-3524
- Volume :
- 30
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neurotoxicity research
- Publication Type :
- Academic Journal
- Accession number :
- 26721795
- Full Text :
- https://doi.org/10.1007/s12640-015-9591-3