CHRONIC ADMINISTRATION OF ANTIPANIC DRUGS ALTERS RAT BRAIN-STEM GABA(A) RECEPTOR SUBUNIT MESSENGER-RNA LEVELS

Mental illnesses, such as panic disorder and depression, display comor bidity as well as common therapeutic treatments. These features point toward a common etiology and/or therapeutic pathway. There is evidence to suggest that some antipanic agents may mediate their effects by al tering gamma-aminobutyric acid (GABA) levels or by modulating the acti vity of the GABA(A) receptor. Chronic stimulation of GABA(A) receptors by agonists or modulators results in changes in the pharmacological p roperties of the receptor concomitant with alterations in the expressi on of specific GABA(A) receptor subunits. Therefore, we investigated t he hypothesis that long-term exposure to three antidepressant/antipani c drugs (imipramine, phenelzine and alprazolam) would produce changes in the steady-state levels of those subunit mRNAs that are believed to encode the major GABA(A) receptor subtype. Further, these changes in gene expression would be different to those produced by the non-antipa nic anxiolytic (buspirone). We report here that, following a 21 day tr eatment, imipramine, phenelzine, alprazolam and buspirone differential ly altered rat brainstem levels of GABA(A) receptor alpha 1-, beta 2- and gamma 2-subunit RNAs. These results demonstrate novel actions of a ntidepressant/antipanic drugs on GABAergic neurotransmission. Copyrigh t (C) 1996 Elsevier Science Ltd.