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

G3 : Genes - Genomes - Genetics
Paola Giusti-RodríguezFei Zou

Abstract

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 (P < 0.001). Furthe...Continue Reading

References

Aug 1, 1990·Pharmacology, Biochemistry, and Behavior·D E BarnesE P Bellows
Jan 1, 1985·Neuroscience and Biobehavioral Reviews·J N Crawley
Apr 17, 2002·Mammalian Genome : Official Journal of the International Mammalian Genome Society·David W ThreadgillRobert W Williams
Nov 2, 2002·The British Journal of Psychiatry : the Journal of Mental Science·Jennifer HallidayRobin McCreadie
Oct 30, 2004·Nature Genetics·Gary A ChurchillUNKNOWN Complex Trait Consortium
Apr 30, 2005·Pharmacogenetics and Genomics·Nikolaos A PatsopoulosJohn P A Ioannidis
Sep 21, 2005·The New England Journal of Medicine·Jeffrey A LiebermanUNKNOWN Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators
Mar 29, 2007·Seminars in Neurology·Karla Soares-Weiser, Hubert H Fernandez
Oct 2, 2008·The British Journal of Psychiatry : the Journal of Mental Science·Del D MillerUNKNOWN Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators
Sep 15, 2010·Nature Reviews. Genetics·Jeffrey T LeekRafael A Irizarry
Dec 18, 2010·Expert Opinion on Drug Metabolism & Toxicology·Jian-Ping Zhang, Anil K Malhotra
Mar 17, 2011·Genome Research·David L AylorGary A Churchill
Mar 18, 2011·ILAR Journal·David W ThreadgillFernando Pardo-Manuel de Villena
Dec 31, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·James J CrowleyPatrick F Sullivan
Jan 18, 2012·Current Opinion in Psychiatry·Thomas M LaursenMogens Vestergaard
Feb 22, 2012·Genetics·UNKNOWN Collaborative Cross Consortium
Mar 3, 2012·G3 : Genes - Genomes - Genetics·Samir N P KeladaFrancis S Collins
Oct 19, 2012·PloS One·Antonio DragoDan Rujescu
Feb 4, 2014·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Allison R RogalaFernando Pardo-Manuel de Villena
Dec 20, 2015·G3 : Genes - Genomes - Genetics·Andrew P MorganFernando Pardo-Manuel de Villena
May 3, 2016·The Journal of Clinical Psychiatry·Martin CloutierEric Wu
Nov 3, 2016·PLoS Pathogens·Jessica B GrahamJennifer M Lund
Jun 9, 2017·Genetics·Anuj SrivastavaFernando Pardo-Manuel de Villena
Jun 21, 2018·Physiological Reports·Rachel C McMullanFernando Pardo-Manuel de Villena

❮ Previous
Next ❯

Methods Mentioned

BETA
dissection
sedation
genotyping

Software Mentioned

SAS
JVC
STAT

Related Concepts

Related Feeds

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here