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Cited by 64Epigenetics and DNA MethylationSchizophrenia research and treatmentNeurotransmitter Receptor Influence on Behavior

Haloperidol treatment induces tissue- and sex-specific changes in DNA methylation: a control study using rats

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Shimabukuro, Morihiro, Jinno, Yoshihiro, Fuke, Chiaki, Okazaki, Yuji·2006·Behavioral and Brain Functions
DOI 10.1186/1744-9081-2-37PMC PMC1684254
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Abstract

Background: We previously found that there is a subtle difference in the global methylation state of blood leukocyte DNA between male subjects with and without schizophrenia. The aim of the current study was to determine whether this difference was a primary effect of the disease state, or a secondary effect of antipsychotics administered to these patients. Methods: We examined the methyl cytosine (mC) content of DNA from the leukocytes, brain, and liver of rats using high performance liquid chromatography. A total of 40 male and female rats received for 21 days daily injection of haloperidol or vehicle solution alone. Results: In control rats injected with buffer only, there was a sex-dependent difference in mC content in leukocyte DNA (male > female;P= 0.028, n = 10), similar to our previous observations in human peripheral leukocytes. No difference in mC content between the sexes was observed in the brain or liver in buffer-treated animals. Haloperidol treatment slightly decreased the mC content of leukocytes in male rats, but unexpectedly, increased the mC content of leukocytes in females. We observed a trend toward a higher level of mC in the liver in both sexes following haloperidol treatment, compared to buffer-treated animals. In contrast, haloperidol treatment resulted in a decrease in mC content in the brain in females, and this difference was statistically significant (P= 0.026). Conclusion: These results indicate that haloperidol can affect DNA methylation states in the brain, as well as in certain other tissues, and raise the possibility that antipsychotic drugs play a role in the observed disparity in mC content in male subjects with and without schizophrenia.

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  • In both human and animal models, treatment with haloperidol induces sex-specific DNA methylation differences.

    “In both human and animal models, it has been observed treatment with haloperidol induces sex-specific DNA methylation differences [71, 72].”

    From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [71]

    The Methods and Discussion report sex-specific DNA methylation responses to haloperidol in male and female rats. The human observations discussed concern methylation differences associated with schizophrenia; this study does not establish that haloperidol induces sex-specific methylation changes in humans. The sentence also cites another source, but only this rat study is assessed here. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Shimabukuro, M., Jinno, Y., Fuke, C., & Okazaki, Y.
Affiliations
  • University of the Ryukyus (JP)
  • Mie University (JP)
Corresponding author
Jinno, Yoshihiro
ORCID
Venue
Behavioral and Brain Functions
Publisher
Springer Science and Business Media LLC
Published
2006-11-29
Volume
2
Issue
1
Pages
37-37
ISSN
1744-9081 (ISSN-L)
DOI
10.1186/1744-9081-2-37
PMC
PMC1684254
OpenAlex
W2158020965
Cited by
64
References
2
Citations by year
2026: 1 · 2024: 3 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 9 · 2013: 4 · 2012: 10
FWCI
1.63
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Behavioral and Brain Functions (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Japan Society for the Promotion of Science (13307027)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
haloperidol, DNA methylation, antipsychotic drugs, sex differences, leukocyte DNA, brain DNA, liver DNA, schizophrenia, epigenetics, rats

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