Common effects of chronically administered antipanic drugs on brainstem gabaa receptor subunit gene expression

ABSTRACT Panic disorder is an anxiety disorder that can be treated by long-term administration of tricyclic antidepressants such as imipramine, monoamine oxidase inhibitors such as

phenelzine, or the selective serotonin reuptake inhibitor (SSRI) antidepressants. Clinical data also indicate that some benzodiazepines, such as alprazolam, are effective antipanic agents,

and that their therapeutic onset is faster than that of antidepressants. Benzodiazepines are well known for their action at GABAA receptors, and preclinical data indicate that imipramine and

phenelzine also interfere with the GABAergic system. In addition some clinical data lend support to decreased benzodiazepine-sensitive receptor function in panic disorder patients. Using

imipramine, phenelzine and alprazolam, we investigated, in rats, the possibility that the therapeutic efficacy of antipanic agents stems from the remodeling of GABAergic transmission in the

pons-medulla region. Of the 12 GABAA receptor subunit (α1–6, β1–3, γ1–3) steady-state mRNA levels investigated, we observed an increase in the levels of the α3-, β1- and γ2-subunit

transcripts with all three antipanic agents tested. The effects of imipramine and phenelzine on these subunits occurred after 21 days of treatment, while alprazolam effects were observed

after 3 days of administration. Histochemical data suggest that the α3β1γ2 subunits comprise a receptor subtype in the pons-medulla region. Therefore, we conclude that these molecular events

parallel the therapeutic profile of the drugs examined. We further propose that these events may correspond to a remodeling of the GABAA receptor population, and may be useful markers for

investigation of the antipanic properties of drugs. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS

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ACKNOWLEDGEMENTS Many thanks to Brian Tancowny and Christine Selzler for their help with the animal procedures. The authors are also grateful to Gail Rauw for her expert technical assistance

with the drug analyses. This work has been supported by the Canadian Psychiatric Research Foundation, the Alberta Mental Health Research Fund and the Medical Research Council of Canada.

VA-MIT was in receipt of a studentship from the Alberta Mental Health Research Fund and ANB is an Alberta Heritage Foundation for Medical Research Scholar. AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Department of Pharmacology, Faculty of Medicine, University of Alberta, Edmonton, T6G 2H7, Alberta, Canada VA-MI Tanay, G B Baker & A N Bateson * Department of Psychiatry,

Faculty of Medicine, University of Alberta, Edmonton, T6G 2H7, Alberta, Canada A J Greenshaw, G B Baker & A N Bateson * Division of Neuroscience, Faculty of Medicine, University of

Alberta, Edmonton, T6G 2H7, Alberta, Canada A J Greenshaw, G B Baker & A N Bateson Authors * VA-MI Tanay View author publications You can also search for this author inPubMed Google

Scholar * A J Greenshaw View author publications You can also search for this author inPubMed Google Scholar * G B Baker View author publications You can also search for this author inPubMed

 Google Scholar * A N Bateson View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to A N Bateson. RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Tanay, VM., Greenshaw, A., Baker, G. _et al._ Common effects of chronically administered antipanic drugs on brainstem GABAA

receptor subunit gene expression. _Mol Psychiatry_ 6, 404–412 (2001). https://doi.org/10.1038/sj.mp.4000879 Download citation * Received: 26 June 2000 * Revised: 22 December 2000 * Accepted:

09 January 2001 * Published: 09 July 2001 * Issue Date: 01 July 2001 * DOI: https://doi.org/10.1038/sj.mp.4000879 SHARE THIS ARTICLE Anyone you share the following link with will be able to

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initiative KEYWORDS * GABAA receptors * subunit * gene expression * antidepressants * panic disorder * pons medulla