Chronic administration of antipanic drugs alters rat brainstem GABA(A) receptor subunit mRNA levels

Mental illnesses, such as panic disorder and depression, display comorbidity 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 altering gamma-aminobutyric acid (GABA) levels or by modulating the activity of the GABA(A) receptor. Chronic stimulation of GABA(A) receptors by agonists or modulators results in changes in the pharmacological properties of the receptor concomitant with alterations in the expression of specific GABA(A) receptor subunits. Therefore, we investigated the hypothesis that long-term exposure to three antidepressant/antipanic 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-antipanic anxiolytic (buspirone). We report here that, following a 21 day treatment, imipramine, phenelzine, alprazolam and buspirone differentially altered rat brainstem levels of GABA(A) receptor alpha 1-, beta 2- and gamma 2-subunit RNAs. These results demonstrate novel actions of antidepressant/antipanic drugs on GABAergic neurotransmission. Copyright (C) 1996 Elsevier Science Ltd.