Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain

Schmitt, A., Zink, M., Petroianu, G., May, B., Braus, D. F., Henn, F. A. (2003) Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain. Neuroscience Letters, 347 (2). pp. 81-4. ISSN 03043940 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/12873733
DOI: 10.1016/S0304-3940(03)00653-0

Abstract

Post-mortem studies in schizophrenic patients revealed alterations in glutamate transporter gene expression. The question concerning a possible influence of chronic antipsychotic treatment on these gene expressions, however, remained open. In this study, 11 rats per group were treated with either haloperidol (1.5 mg/kg per day) or clozapine (45 mg/kg per day) over a period of 6 months in doses comparable to clinic application. Gene expression of glial glutamate transporter EAAT2 and the predominantly neuronal glutamate transporter EAAT3 were examined by in situ hybridization. Clozapine significantly downregulated EAAT2 in hippocampal CA1 and parietal cortex and EAAT3 in the cingulate cortex compared to the expression upon haloperidol treatment and controls. Additionally, clozapine decreased EAAT2 in temporal, cingulate and frontal cortex and downregulated EAAT3 in cingulate and infralimbic cortex, striatum and hippocampal CA1 and CA2 compared to controls. Haloperidol downregulated EAAT2 in cingulate and frontal cortex and reduced EAAT3 in nucleus accumbens, infralimbic cortex and hippocampal CA2. We hypothesize that glutamate transporter downregulation by neuroleptics increases glutamatergic action at the postsynaptic neuron and thereby may be related to beneficial antipsychotic effects and side effects.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Transport System X-AG/genetics/ metabolism Animals Antipsychotic Agents/administration & dosage/ pharmacology Brain/ drug effects/metabolism Clozapine/pharmacology Down-Regulation Excitatory Amino Acid Transporter 2/genetics/ metabolism Excitatory Amino Acid Transporter 3 Glutamate Plasma Membrane Transport Proteins Haloperidol/pharmacology In Situ Hybridization Male Neuroglia/ drug effects/metabolism Neurons/ drug effects/metabolism Rats Rats, Sprague-Dawley Symporters/genetics/ metabolism Time Factors
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders > mental disorders > personality disorders
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types
organs, tissues, organelles, cell types and functions > cell types and functions > cell types

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > glia cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > glia cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > glia cells

organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

organs, tissues, organelles, cell types and functions > tissues types and functions > transport
CSHL Authors:
Communities: CSHL labs > Henn lab
Depositing User: Matt Covey
Date Deposited: 11 Jun 2013 18:46
Last Modified: 11 Jun 2013 18:46
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27959

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