Decreased gene expression of glial and neuronal glutamate transporters after chronic antipsychotic treatment in rat brain.
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.
Schmitt
Andrea
A
Central Institute of Mental Health, PO Box 122120, D-68072 Mannheim, Germany. schmitt@zi-mannheim.de
Zink
Mathias
M
Petroianu
Georg
G
May
Brigitte
B
Braus
Dieter F
DF
Henn
Fritz A
FA
D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology; D015536:Down-Regulation; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; D006220:Haloperidol / Q000494:pharmacology; D017403:In Situ Hybridization; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D027322:Amino Acid Transport System X-AG; D014150:Antipsychotic Agents; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D050491:Glutamate Plasma Membrane Transport Proteins; C493398:Slc1a1 protein, rat; C493395:Slc1a2 protein, rat; D027981:Symporters; D003024:Clozapine; D006220:Haloperidol