Cited by 189Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

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Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia

Szumlinski, K. K., Lominac, K. D., Kleschen, M. J., Oleson, E. B., Dehoff, M. H., Schwartz, M. K., Seeberg, P. H., Worley, P. F., Kalivas, P. W.·2005·Genes, Brain and Behavior

DOI 10.1111/j.1601-183x.2005.00120.x

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Abstract

Homer proteins are involved in the functional assembly of postsynaptic density proteins at glutamatergic synapses and are implicated in learning, memory and drug addiction. Here, we report that Homer1-knockout (Homer1-KO) mice exhibit behavioral and neurochemical abnormalities that are consistent with the animal models of schizophrenia. Relative to wild-type mice, Homer1-KO mice exhibited deficits in radial arm maze performance, impaired prepulse inhibition, enhanced 'behavioral despair', increased anxiety in a novel objects test, enhanced reactivity to novel environments, decreased instrumental responding for sucrose and enhanced MK-801- and methamphetamine-stimulated motor behavior. No-net-flux in vivo microdialysis revealed a decrease in extracellular glutamate content in the nucleus accumbens and an increase in the prefrontal cortex. Moreover, in Homer1-KO mice, cocaine did not stimulate a rise in frontal cortex extracellular glutamate levels, suggesting hypofrontality. These behavioral and neurochemical data derived from Homer1 mutant mice are consistent with the recent association of schizophrenia with a single-nucleotide polymorphism in the Homer1 gene and suggest that the regulation of extracellular levels of glutamate within limbo-corticostriatal structures by Homer1 gene products may be involved in the pathogenesis of this neuropsychiatric disorder.

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Authors: Szumlinski, K. K., Lominac, K. D., Kleschen, M. J., Oleson, E. B., Dehoff, M. H., Schwartz, M. K., Seeberg, P. H., Worley, P. F., & Kalivas, P. W.
Affiliations: Medical University of South Carolina (US)
Johns Hopkins University (US)
Max Planck Institute for Medical Research (DE)
Corresponding author: Szumlinski, K. K.
ORCID: Szumlinski, K. K.
Lominac, K. D.
Oleson, E. B.
Worley, P. F.
Kalivas, P. W.
Venue: Genes, Brain and Behavior
Publisher: Wiley
Published: 2005-02-08
Volume: 4
Issue: 5
Pages: 273-288
ISSN: 1601-183X (ISSN-L)
1601-1848
DOI: 10.1111/j.1601-183x.2005.00120.x
OpenAlex: W2069755036
Cited by: 181
References: 57
Citations by year: 2025: 5 · 2024: 8 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 8 · 2019: 4 · 2018: 6 · 2017: 10 · 2016: 6 · 2015: 9 · 2014: 8 · 2013: 16 · 2012: 9
FWCI: 8.02
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Genes Brain & Behavior (publishedVersion)
PubMed (publishedVersion)
Max Planck Institute for Plasma Physics (submittedVersion)
Max Planck Digital Library (submittedVersion)
MPG.PuRe (Max Planck Society) (submittedVersion)
Funders: National Institute of Mental Health (R01MH040817, MH-40817)
National Institute on Drug Abuse (DA14185, DA 11742, R21DA014185, R01DA011742)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: Homer1, schizophrenia, postsynaptic density, glutamatergic synapses, prepulse inhibition, anxiety, behavioral despair, sucrose preference, glutamate, nucleus accumbens, prefrontal cortex, hypofrontality, single nucleotide polymorphisms, animal models of schizophrenia
MeSH terms: Homer Scaffolding Proteins, Animals, Behavior, Animal, Carrier Proteins, Conditioning, Operant, Exploratory Behavior, Female, Frontal Lobe, Humans, Male, Mice, Inbred C57BL, Neural Inhibition, Nucleus Accumbens, Phenotype, Schizophrenia, Gene Deletion, Mice, Knockout, Glutamic Acid, Maze Learning, Polymorphism, Single Nucleotide, Mice

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Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia

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