Cited by 91Neurotransmitter Receptor Influence on BehaviorHistone Deacetylase Inhibitors ResearchNeuroscience and Neuropharmacology Research

Additive effects of histone deacetylase inhibitors and amphetamine on histone H4 acetylation, cAMP responsive element binding protein phosphorylation and ΔFosB expression in the striatum and locomotor sensitization in mice

Shen, H.-Y., Kalda, A., Yu, L., Ferrara, J., Zhu, J., Chen, J.-F.·2008·Neuroscience

Abstract

Histone deacetylase (HDAC) plays an important role in chromatin remodeling in response to a variety of neurochemical signalings and behavioral manipulations, and may be a therapeutic target for modulation of psychostimulant behavioral sensitization. In this study, we investigated the molecular interaction between histone deacetylase inhibitor (HDACi) and psychostimulant in vivo of mice after repeated treatment with the HDACi, butyric acid (BA) and valproic acid (VPA), alone or in combination with amphetamine. Repeated treatment with amphetamine produced HDACi-like effects: enhanced global histone H4 acetylation level by Western blot as well as specific histone H4 acetylation associated with fosB promoter by chromatin immunoprecipitation in the striatum. Conversely, repeated treatment with BA or VPA produced amphetamine-like effects: enhanced cAMP responsive element binding protein (CREB) phosphorylation at Ser(133) position and increased DeltaFosB protein levels in the striatum. Furthermore, co-administration of BA or VPA with amphetamine produced additive effects on histone H4 acetylation as well as CREB phosphorylation in the striatum. The interplay of HDAC and CREB was also supported by co-immunoprecipitation assays demonstrating that repeated treatment with VPA reduced the association of CREB and HDAC1 in the striatum. Finally, the additive effect of VPA/BA and amphetamine on histone H4 acetylation, phosphorylated CREB, and DeltaFosB was associated with potentiated amphetamine-induced locomotor activity. Thus, HDACi may interact additively with psychostimulants at both histone acetylation and CREB phosphorylation through the CREB:HDAC protein complex in the striatum to modulate DeltaFosB protein levels and psychomotor behavioral sensitization.

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Crossref · 10.1016/j.neuroscience.2008.09.019

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Authors
Shen, H.-Y., Kalda, A., Yu, L., Ferrara, J., Zhu, J., & Chen, J.-F.
Affiliations
Boston University (US)
Corresponding author
Chen, J.-F.
Venue
Neuroscience
Publisher
Elsevier BV
Published
2008-12
Volume
157
Issue
3
Pages
644-655
ISSN
0306-4522 (ISSN-L)
OpenAlex
W2080792460
Cited by
91
References
58
Citations by year
2025: 3 · 2024: 5 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 1 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 10 · 2013: 6 · 2012: 5
FWCI
1.59
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institute on Drug Abuse (R01DA019362, DA19362)
  • National Institute of Neurological Disorders and Stroke (R01NS041083, NS41083)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
histone deacetylase inhibitors, amphetamine, histone H4 acetylation, CREB phosphorylation, ΔFosB, striatum, locomotor sensitization, butyrate, valproic acid, chromatin remodeling, additive drug effects
MeSH terms
Acetylation, Amphetamine, Central Nervous System Stimulants, Animals, Corpus Striatum, Drug Interactions, Enzyme Inhibitors, Histones, Male, Mice, Inbred C57BL, Motor Activity, Phosphorylation, Time Factors, Valproic Acid, Gene Expression, Proto-Oncogene Proteins c-fos, Butyric Acid, Chromatin Immunoprecipitation, CREB-Binding Protein, Mice

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