Chronic administration of antipanic drugs alters rat brainstem GABAA receptor subunit mRNA levels.
Mental illness, 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 GABAA receptor. Chronic stimulation of GABAA receptors by agonists or modulators results in changes in the pharmacological properties of the receptor concomitant with alterations in the expression of specific GABAA 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 GABAA 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 GABAA receptor alpha 1-, beta 2- and gamma 2-subunit RNAs. These results demonstrate novel actions of antidepressant/antipanic drugs on GABAergic neurotransmission.
Tanay
V A
VA
Department of Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Glencorse
T A
TA
Greenshaw
A J
AJ
Baker
G B
GB
Bateson
A N
AN
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002065:Buspirone / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D007099:Imipramine / Q000494:pharmacology; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D016584:Panic Disorder / Q000188:drug therapy*; D010624:Phenelzine / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis*
D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D008996:Monoamine Oxidase Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D010624:Phenelzine; D007099:Imipramine; D002065:Buspirone