Pharmacopsychiatry 2004; 37(4): 171-174
DOI: 10.1055/s-2004-827173
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Differential Effects of Long-Term Treatment with Clozapine or Haloperidol on GABA Transporter Expression

M. Zink1 , A. Schmitt1 , B. May1 , B. Müller1 , D. F. Braus1 , F. A. Henn1
  • 1Central Institute of Mental Health, Department of Psychiatry, Mannheim, Germany
Further Information

Publication History

Received: 5.3.2003 Revised: 16.5.2003

Accepted: 6.6.2003

Publication Date:
01 July 2004 (online)

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

P.O. Box 12 21 20

68072 Mannheim

Germany

Phone: +49 621 1703 125

Fax: +49 621 23429

Email: zink@kv.zi-mannheim.de