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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

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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.

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Acknowledgments

The authors wish to thank Ezekiell Mouzon at Mount Sinai School of Medicine for graciously donating HDAC2 floxed mice.

Funding

This study was supported by funds of the Intramural Research Program of the DHHS/NIH/NIDA.

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Authors and Affiliations

  1. Molecular Neuropsychiatry Research Branch, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA

    Oscar V. Torres, Bruce Ladenheim, Subramaniam Jayanthi, Michael T. McCoy, Irina N. Krasnova & Jean Lud Cadet

  2. Transgenic Core Facility, DHHS/NIH/NIDA Intramural Research Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD, 21224, USA

    Francois A. Vautier

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  1. Oscar V. Torres
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  2. Bruce Ladenheim
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  3. Subramaniam Jayanthi
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  5. Irina N. Krasnova
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  6. Francois A. Vautier
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  7. Jean Lud Cadet
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Correspondence to Jean Lud Cadet.

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Torres, O.V., Ladenheim, B., Jayanthi, S. et al. An Acute Methamphetamine Injection Downregulates the Expression of Several Histone Deacetylases (HDACs) in the Mouse Nucleus Accumbens: Potential Regulatory Role of HDAC2 Expression. Neurotox Res 30, 32–40 (2016). https://doi.org/10.1007/s12640-015-9591-3

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