ArticlePsychopharmacology2017
Histone deacetylase inhibitors reverse age-related increases in side effects of haloperidol in mice.
Article in Psychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- DNA methylation and histone modifications associated with antipsychotic treatment: a systematic review.Molecular psychiatry · 2025Pooled it
- Impact of 5-HT7 receptor gene deletion on memory and affective behaviors in young and aged mice.Neuroscience · 2026Article
- The impact of sex on memory during aging and Alzheimer's disease progression: Epigenetic mechanisms.Journal of Alzheimer's disease : JAD · 2024Review
- Class 1 histone deacetylases differentially modulate memory and synaptic genes in a spatial and temporal manner in aged and APP/PS1 mice.Brain research · 2024Article
- Distinguishing features of depression in dementia from primary psychiatric disease.Discover mental health · 2024Review
- Pharmacological inhibition of plasminogen activator inhibitor-1 prevents memory deficits and reduces neuropathology in APP/PS1 mice.Psychopharmacology · 2023Article
- Histone deacetylase 1 regulates haloperidol-induced motor side effects in aged mice.Behavioural brain research · 2023Article
- Histone deacetylase inhibitors mitigate antipsychotic risperidone-induced motor side effects in aged mice and in a mouse model of Alzheimer's disease.Frontiers in psychiatry · 2022Article
- Dose Effects of Histone Deacetylase Inhibitor Tacedinaline (CI-994) on Antipsychotic Haloperidol-Induced Motor and Memory Side Effects in Aged Mice.Frontiers in neuroscience · 2021Article
- The Hyperactivity-Impulsivity-Irritiability-Disinhibition-Aggression-Agitation Domain in Alzheimer's Disease: Current Management and Future Directions.Frontiers in pharmacology · 2019Review
- A translational perspective on histone acetylation modulators in psychiatric disorders.Psychopharmacology · 2018Review
- Epigenetic Alterations Impact on Antipsychotic Treatment in Elderly Patients.Current treatment options in psychiatry · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOlder patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility.
methodsIn this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects. In addition, we pretreated separate groups of young and aged mice with histone deacetylase (HDAC) inhibitors valproic acid (VPA) or entinostat (MS-275) and then administered HAL.
resultsOur results show that the motor side effects of HAL are exaggerated in aged mice as compared to young mice and that HDAC inhibitors are able to reverse the severity of these deficits. HAL-induced motor deficits in aged mice are associated with an age- and drug-dependent decrease in striatal D2R protein levels and functionality. Further, histone acetylation was reduced while histone tri-methylation was increased at specific lysine residues of H3 and H4 within the Drd2 promoter in the striatum of aged mice. HDAC inhibitors, particularly VPA, restored striatal D2R protein levels and functionality and reversed age- and drug-related histone modifications at the Drd2 promoter.
conclusionsThese results suggest that epigenetic changes at the striatal Drd2 promoter drive age-related increases in antipsychotic side effect susceptibility, and HDAC inhibitors may be an effective adjunct treatment strategy to reduce side effects in aged populations.
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