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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 357, Issue 1, pp 32–38 | Cite as

Effects of phenelzine and imipramine on the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase in rat cortex

  • Chien-Tsai Lai
  • Véronique A.-M. I. Tanay
  • Gregory J. R. Charrois
  • Glen B. Baker
  • A. N. Bateson
Original article

Abstract

There is an increasing body of evidence suggesting that GABA plays an important role in the therapeutic effects of antidepressant/antipanic drugs. Phenelzine and imipramine are efficacious in the treatment of depression and panic disorder and phenelzine has been reported to elevate GABA levels while imipramine enhances GABA release in rat brains. In the present study, using a multiprobe quantitative solution hybridization assay, we measured the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD67 and GAD65), the GABA transporter GAT-1 and GABA transaminase (GABA-T) in rat cortex after treatment with constant infusion (via osmotic minipumps) of phenelzine or imipramine for a short-term (3 days) or long-term (21 days) period. We found that none of the treatments gave rise to significant changes in the steady-state levels of mRNAs encoding GAD67, GAD65 or GABA-T at any time point. The steady-state levels of GAT-1 mRNA were increased significantly (23%) after long-term, but not by short-term, treatment with phenelzine. Imipramine treatment, short- or long-term, did not alter the steady-state levels of GAT-1 mRNA. These results suggest that the GABA enhancing effects of phenelzine or imipramine in rat cortex do not affect the steady-state levels of mRNAs that encode GAD67, GAD65 and GABA-T. Further, the previously observed increases in GABA levels or GABA release induced by these drugs are probably not a consequence of changes in the expression of these genes.

Key words Phenelzine Imipramine GABA Glutamic acid decarboxylase GABA transporter GABA transaminase mRNA Gene expression 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Chien-Tsai Lai
    • 1
  • Véronique A.-M. I. Tanay
    • 2
  • Gregory J. R. Charrois
    • 2
  • Glen B. Baker
    • 1
  • A. N. Bateson
    • 2
  1. 1.Neurochemical Research Unit, Department of Psychiatry, 1E7.44 W. Mackenzie Health Sciences Center, University of Alberta, Edmonton, Alberta, T6G 2B7 CanadaCA
  2. 2.Department of Pharmacology, University of Alberta, Edmonton, Alberta, T6G 2B7 CanadaCA

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