ArticlePharmacological reports : PR2025
A single dose of haloperidol decanoate induces short-term hippocampal neuroinflammation: focus on the glial response.
Article in Pharmacological reports : PR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Curcumin Ameliorates Depressive-like Behaviors by Modulating mGluR2/PGC-1α-Mediated Glutamatergic Homeostasis and Mitochondrial Function.Molecular neurobiology · 2025Article
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12 authors.
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Abstract
backgroundHaloperidol is a widely used antipsychotic for the treatment of neuropsychiatric disorders, the pathophysiology of which may involve hippocampal alterations. Hippocampus is affected by long-term use of the drug, but the effects of acute doses on the hippocampus remain unclear. The present study investigated whether a single dose of haloperidol decanoate could induce short-term hippocampal neuroinflammation and changes in cholinergic, glutamatergic and redox homeostasis in adult rats, focusing on the glial response.
methodsMale Wistar rats (60 days old) received a single intramuscular injection of haloperidol decanoate (38 mg/kg) or vehicle. After 7 days, hippocampal tissue was used to assess gene expression of inflammatory mediators, glutamate transporters, and transcriptional factors that regulate neuroinflammation. The enzymatic activities of acetylcholinesterase (AChE), glutamine synthetase (GS), and glutathione peroxidase (GPx), and glutamate uptake and reduced glutathione (GSH) levels were also determined.
resultsHaloperidol decanoate increased the gene expression of pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Moreover, downregulation of the transcriptional factor erythroid 2-related factor 2 (Nrf2) and the peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) was observed. In contrast, nuclear factor κB (NFκB) transcriptional levels remained unchanged. Haloperidol also increased glutamate uptake, the glutamate transporter GLAST gene expression, and the AChE and GPx activities.
conclusionsOur findings show that a single dose of haloperidol decanoate induces short-term hippocampal neuroinflammation and changes in glial parameters, highlighting the need for future adjuvant glioprotective strategies that can attenuate these effects.
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