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

Genes Brain Behav. 2005 Jul;4(5):273-88. doi: 10.1111/j.1601-183X.2005.00120.x.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Conditioning, Operant / physiology
  • Exploratory Behavior / physiology
  • Female
  • Frontal Lobe / metabolism*
  • Gene Deletion
  • Glutamic Acid / metabolism*
  • Homer Scaffolding Proteins
  • Humans
  • Male
  • Maze Learning / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Inhibition / physiology
  • Nucleus Accumbens / metabolism*
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Schizophrenia / genetics
  • Schizophrenia / metabolism


  • Carrier Proteins
  • HOMER1 protein, human
  • Homer Scaffolding Proteins
  • Homer1 protein, mouse
  • Glutamic Acid