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Antipsychotic‐induced gene regulation in multiple brain regions
Author(s) -
Girgenti Matthew James,
Nisenbaum Laura K.,
Bymaster Franklin,
Terwilliger Rosemarie,
Duman Ronald S,
Newton Samuel Sathyanesan
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06585.x
Subject(s) - biology , olanzapine , striatum , metabotropic receptor , metabotropic glutamate receptor 5 , pharmacology , metabotropic glutamate receptor , neuroscience , receptor , dopamine , glutamate receptor , genetics , psychology , schizophrenia (object oriented programming) , psychiatry
J. Neurochem. (2010) 10.1111/j.1471‐4159.2010.06585.x Abstract The molecular mechanism of action of antipsychotic drugs is not well understood. Their complex receptor affinity profiles indicate that their action could extend beyond dopamine receptor blockade. Single gene expression studies and high‐throughput gene profiling have shown the induction of genes from several molecular classes and functional categories. Using a focused microarray approach, we investigated gene regulation in rat striatum, frontal cortex, and hippocampus after chronic administration of haloperidol or olanzapine. Regulated genes were validated by in situ hybridization, real‐time PCR, and immunohistochemistry. Only limited overlap was observed in genes regulated by haloperidol and olanzapine. Both drugs elicited maximal gene regulation in the striatum and least in the hippocampus. Striatal gene induction by haloperidol was predominantly in neurotransmitter signaling, G‐protein coupled receptors, and transcription factors. Olanzapine prominently induced retinoic acid and trophic factor signaling genes in the frontal cortex. The data also revealed the induction of several genes that could be targeted in future drug development efforts. The study uncovered the induction of several novel genes, including somatostatin receptors and metabotropic glutamate receptors. The results demonstrating the regulation of multiple receptors and transcription factors suggests that both typical and atypical antipsychotics could possess a complex molecular mechanism of action.