The effects of haloperidol on microglial morphology and translocator protein levels: An in vivo study in rats using an automated cell evaluation pipeline

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Title: The effects of haloperidol on microglial morphology and translocator protein levels: An in vivo study in rats using an automated cell evaluation pipeline
Authors: Bloomfield, PS
Bonsall, D
Wells, L
Dormann, D
Howes, O
De Paola, V
Item Type: Journal Article
Abstract: BACKGROUND: Altered microglial markers and morphology have been demonstrated in patients with schizophrenia in post-mortem and in vivo studies. However, it is unclear if changes are due to antipsychotic treatment. AIMS: Here we aimed to determine whether antipsychotic medication affects microglia in vivo. METHODS: To investigate this we administered two clinically relevant doses (0.05 mg n=12 and 2.5 mg n=7 slow-release pellets, placebo n=20) of haloperidol, over 2 weeks, to male Sprague Dawley rats to determine the effect on microglial cell density and morphology (area occupied by processes and microglial cell area). We developed an analysis pipeline for the automated assessment of microglial cells and used lipopolysaccharide (LPS) treatment ( n=13) as a positive control for analysis. We also investigated the effects of haloperidol ( n=9) or placebo ( n=10) on the expression of the translocator protein 18 kDa (TSPO) using autoradiography with [3H]PBR28, a TSPO ligand used in human positron emission tomography (PET) studies. RESULTS: Here we demonstrated that haloperidol at either dose does not alter microglial measures compared with placebo control animals ( p > 0.05). Similarly there was no difference in [3H]PBR28 binding between placebo and haloperidol tissue ( p > 0.05). In contrast, LPS was associated with greater cell density ( p = 0.04) and larger cell size ( p = 0.01). CONCLUSION: These findings suggest that haloperidol does not affect microglial cell density, morphology or TSPO expression, indicating that clinical study alterations are likely not the consequence of antipsychotic treatment. The automated cell evaluation pipeline was able to detect changes in microglial morphology induced by LPS and is made freely available for future use.
Issue Date: 1-Nov-2018
Date of Acceptance: 11-Jun-2018
URI: http://hdl.handle.net/10044/1/69249
DOI: https://dx.doi.org/10.1177/0269881118788830
ISSN: 1461-7285
Publisher: SAGE Publications
Start Page: 1264
End Page: 1272
Journal / Book Title: Journal of Psychopharmacology
Volume: 32
Issue: 11
Copyright Statement: © The Author(s) 2018. Published by Sage Publications. The final, definitive version of this paper has been published in Journal of Psychopharmacology by Sage Publications Ltd. All rights reserved. It is available at: https://journals.sagepub.com/doi/10.1177/0269881118788830
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 607616
Keywords: Science & Technology
Life Sciences & Biomedicine
Clinical Neurology
Neurosciences
Pharmacology & Pharmacy
Psychiatry
Neurosciences & Neurology
Microglia
neuroinflammation
haloperidol
LPS
TSPO
morphology
PERIPHERAL BENZODIAZEPINE-RECEPTORS
ULTRA-HIGH RISK
1ST-EPISODE PSYCHOSIS
ACTIVATION
SCHIZOPHRENIA
BRAIN
PET
ARIPIPRAZOLE
DENSITY
NEUROINFLAMMATION
11 Medical and Health Sciences
17 Psychology and Cognitive Sciences
Publication Status: Published
Conference Place: United States
Online Publication Date: 2018-08-21
Appears in Collections:Clinical Sciences
Imaging Sciences
Molecular Sciences
Faculty of Medicine



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