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DOI: 10.1055/s-2004-827173
Differential Effects of Long-Term Treatment with Clozapine or Haloperidol on GABA Transporter Expression
Publikationsverlauf
Received: 5.3.2003
Revised: 16.5.2003
Accepted: 6.6.2003
Publikationsdatum:
01. Juli 2004 (online)
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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.
References
- 1 Adler G, Grieshaber S, Faude V, Thebaldi B, Dressing H. Clozapine in patients with chronic schizophrenia: Serum level, EEG and memory performance. Pharmacopsychiatry. 2002; 35 190-194
- 2 Akbarian S, Kim J J, Potkin S G, Hagman J O, Tafazzoli A, Bunney W E Jr,. et al . Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry. 1995; 52 258-266
Dr. med. Mathias Zink
Central Institute of Mental Health
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Germany
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