EFFECTS OF PHENELZINE AND IMIPRAMINE ON THE STEADY-STATE LEVELS OF MESSENGER-RNAS THAT ENCODE GLUTAMIC-ACID DECARBOXYLASE (GAD(67) AND GAD(65)), THE GABA TRANSPORTER GAT-1 AND GABA TRANSAMINASE IN RAT CORTEX

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 d epression and panic disorder and phenelzine has been reported to eleva te GABA levels while imipramine enhances GABA release in rat brains. I n the present study, using a multiprobe quantitative solution hybridiz ation assay, we measured the steady-state levels of mRNAs that encode glutamic acid decarboxylase (GAD(67) and GAD(65)), the GABA transporte r GAT-1 and GABA transaminase (GABA-T) in rat cortex after treatment w ith constant infusion (via osmotic minipumps) of phenelzine or imipram ine 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 st eady-state levels of mRNAs encoding GAD(67), GAD(65) Or GABA-T at any time point. The steady-state levels of GAT-1 mRNA were increased signi ficantly (23%) after long-term, but not by short-term, treatment with phenelzine. Imipramine treatment, short- or long-term, did not alter t he steady-state levels of GAT-1 mRNA. These results suggest that the G ABA enhancing effects of phenelzine or imipramine in rat cortex do not affect the steady-state levels of mRNAs that encode GAD(67), GAD(65) 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.