title: An Acute Methamphetamine Injection Downregulates the Expression of Several Histone Deacetylases (HDACs) in the Mouse Nucleus Accumbens: Potential Regulatory Role of HDAC2 Expression.
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.
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
authors.forename: Oscar V
authors.initials: OV
authors.lastname: Torres
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Ladenheim
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Jayanthi
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: McCoy
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
authors.forename: Irina N
authors.initials: IN
authors.lastname: Krasnova
authors.affiliation: Transgenic Core Facility, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA.
authors.forename: Francois A
authors.initials: FA
authors.lastname: Vautier
authors.affiliation: Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA. jcadet@intra.nida.nih.gov.
authors.forename: Jean Lud
authors.initials: JL
authors.lastname: Cadet
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D056464:Histone Deacetylase 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008694:Methamphetamine; C533424:Hdac2 protein, mouse; D056464:Histone Deacetylase 2
keywords: Epigenetics; HDAC2; Histone deacetylase; Knockout-mouse; Methamphetamine; Nucleus accumbens