Differential effects of long-term treatment with clozapine or haloperidol on GABA transporter expression

Zink, M., Schmitt, A., May, B., Muller, B., Braus, D. F., Henn, F. A. (July 2004) Differential effects of long-term treatment with clozapine or haloperidol on GABA transporter expression. Pharmacopsychiatry, 37 (4). pp. 171-4. ISSN 0176-3679 (Print)0176-3679 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/15467974
DOI: 10.1055/s-2004-827173

Abstract

BACKGROUND: Post-mortem studies with brain samples of schizophrenic patients led revealed altered GABA-ergic markers like reduced expression of the GABA transporter GAT-1. Whether this effect is due to the pathophysiology of schizophrenia or to antipsychotic treatment has not been investigated. We therefore established an animal trial of long-term antipsychotic treatment to address this question. METHODS: A total of 33 adult male rats were investigated in three cohorts of 11 animals. One group received clozapine (45 mg/kg/ day), another group haloperidol (1.5 mg/kg/day), and the third one pH-adapted water over a period of 6 months. In situ hybridization with cRNA probes specific for GABA transporters VGAT, GAT-1 and GAT-3 were performed in comparison to control animals. RESULTS: While GAT-1 was upregulated, VGAT expression declined in cortical and limbic brain regions, whereby haloperidol showed a greater effect than clozapine. GAT-3 expression was suppressed in parietal and temporal cortex. CONCLUSIONS: We thus conclude that long-term antipsychotic treatment alters GABA transporter expression in rat. The upregulation of GAT-1 contrasts with the post-mortem finding of reduced GAT-1 expression in schizophrenic patients. Our results facilitate the distinction between disease dependent changes of GABAergic markers and medication effects.

Item Type: Paper
Additional Information:
Uncontrolled Keywords: Amino Acid Transport Systems/drug effects/genetics/metabolism Animals Antipsychotic Agents/administration & dosage/ pharmacology Brain/anatomy & histology/drug effects/metabolism Clozapine/administration & dosage/ pharmacology Drug Administration Schedule GABA Plasma Membrane Transport Proteins Haloperidol/administration & dosage/ pharmacology In Situ Hybridization Male Membrane Transport Proteins/ drug effects/genetics/ metabolism RNA, Complementary/drug effects/genetics Rats Rats, Sprague-Dawley Time Factors Vesicular Inhibitory Amino Acid Transport Proteins Vesicular Transport Proteins/drug effects/genetics/metabolism Water/administration & dosage
Subjects: diseases & disorders
bioinformatics > genomics and proteomics > small molecules > GABA
bioinformatics > genomics and proteomics
diseases & disorders > mental disorders
bioinformatics > genomics and proteomics > small molecules
CSHL Authors:
Communities: CSHL labs > Henn lab
Depositing User: Matt Covey
Date: July 2004
Date Deposited: 04 Mar 2013 20:57
Last Modified: 04 Mar 2013 20:57
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27715

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