Antipsychotic Behavioral Phenotypes in the Mouse Collaborative Cross Recombinant Inbred Inter-Crosses (RIX).


Journal

G3 (Bethesda, Md.)
ISSN: 2160-1836
Titre abrégé: G3 (Bethesda)
Pays: England
ID NLM: 101566598

Informations de publication

Date de publication:
02 09 2020
Historique:
pubmed: 23 7 2020
medline: 22 6 2021
entrez: 23 7 2020
Statut: epublish

Résumé

Schizophrenia is an idiopathic disorder that affects approximately 1% of the human population, and presents with persistent delusions, hallucinations, and disorganized behaviors. Antipsychotics are the standard pharmacological treatment for schizophrenia, but are frequently discontinued by patients due to inefficacy and/or side effects. Chronic treatment with the typical antipsychotic haloperidol causes tardive dyskinesia (TD), which manifests as involuntary and often irreversible orofacial movements in around 30% of patients. Mice treated with haloperidol develop many of the features of TD, including jaw tremors, tongue protrusions, and vacuous chewing movements (VCMs). In this study, we used genetically diverse Collaborative Cross (CC) recombinant inbred inter-cross (RIX) mice to elucidate the genetic basis of antipsychotic-induced adverse drug reactions (ADRs). We performed a battery of behavioral tests in 840 mice from 73 RIX lines (derived from 62 CC strains) treated with haloperidol or placebo in order to monitor the development of ADRs. We used linear mixed models to test for strain and treatment effects. We observed highly significant strain effects for almost all behavioral measurements investigated (

Identifiants

pubmed: 32694196
pii: g3.120.400975
doi: 10.1534/g3.120.400975
pmc: PMC7466989
doi:

Substances chimiques

Antipsychotic Agents 0
Haloperidol J6292F8L3D

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3165-3177

Subventions

Organisme : NIEHS NIH HHS
ID : P42 ES031007
Pays : United States
Organisme : NHGRI NIH HHS
ID : P50 HG006582
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH090338
Pays : United States

Informations de copyright

Copyright © 2020 Giusti-Rodriguez et al.

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Auteurs

Paola Giusti-Rodríguez (P)

Department of Genetics, University of North Carolina, Chapel Hill, NC.

James G Xenakis (JG)

Department of Genetics, University of North Carolina, Chapel Hill, NC.

James J Crowley (JJ)

Department of Genetics, University of North Carolina, Chapel Hill, NC.

Randal J Nonneman (RJ)

Department of Genetics, University of North Carolina, Chapel Hill, NC.

Daniela M DeCristo (DM)

Department of Genetics, University of North Carolina, Chapel Hill, NC.

Allison Ryan (A)

Department of Genetics, University of North Carolina, Chapel Hill, NC.

Corey R Quackenbush (CR)

Department of Genetics, University of North Carolina, Chapel Hill, NC.

Darla R Miller (DR)

Department of Genetics, University of North Carolina, Chapel Hill, NC.

Ginger D Shaw (GD)

Department of Genetics, University of North Carolina, Chapel Hill, NC.

Vasyl Zhabotynsky (V)

Department of Biostatistics, University of North Carolina, Chapel Hill, NC.

Patrick F Sullivan (PF)

Department of Genetics, University of North Carolina, Chapel Hill, NC fzou@bios.unc.edu fernando_pardo-manuel@med.unc.edu patrick_sullivan@med.unc.edu.
Department of Psychiatry, University of North Carolina, Chapel Hill, NC.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Fernando Pardo Manuel de Villena (FP)

Department of Genetics, University of North Carolina, Chapel Hill, NC fzou@bios.unc.edu fernando_pardo-manuel@med.unc.edu patrick_sullivan@med.unc.edu.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.

Fei Zou (F)

Department of Genetics, University of North Carolina, Chapel Hill, NC fzou@bios.unc.edu fernando_pardo-manuel@med.unc.edu patrick_sullivan@med.unc.edu.
Department of Biostatistics, University of North Carolina, Chapel Hill, NC.

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