| First Author | Szumlinski KK | Year | 2005 |
| Journal | Genes Brain Behav | Volume | 4 |
| Issue | 5 | Pages | 273-88 |
| PubMed ID | 16011574 | Mgi Jnum | J:114304 |
| Mgi Id | MGI:3688761 | Doi | 10.1111/j.1601-183X.2005.00120.x |
| Citation | Szumlinski KK, et al. (2005) Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia. Genes Brain Behav 4(5):273-88 |
| abstractText | 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. |
