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Review ArticleReview Article

Targeting the Modulation of Neural Circuitry for the Treatment of Anxiety Disorders

David H. Farb and Marcia H. Ratner
Leslie A. Morrow, ASSOCIATE EDITOR
Pharmacological Reviews October 2014, 66 (4) 1002-1032; DOI: https://doi.org/10.1124/pr.114.009126
David H. Farb
Laboratory of Molecular Neurobiology, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts
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Marcia H. Ratner
Laboratory of Molecular Neurobiology, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts
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Leslie A. Morrow
Laboratory of Molecular Neurobiology, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts
Roles: ASSOCIATE EDITOR
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Abstract

Anxiety disorders are a major public health concern. Here, we examine the familiar area of anxiolysis in the context of a systems-level understanding that will hopefully lead to revealing an underlying pharmacological connectome. The introduction of benzodiazepines nearly half a century ago markedly improved the treatment of anxiety disorders. These agents reduce anxiety rapidly by allosterically enhancing the postsynaptic actions of GABA at inhibitory type A GABA receptors but side effects limit their use in chronic anxiety disorders. Selective serotonin reuptake inhibitors and serotonin/norepinephrine reuptake inhibitors have emerged as an effective first-line alternative treatment of such anxiety disorders. However, many individuals are not responsive and side effects can be limiting. Research into a relatively new class of agents known as neurosteroids has revealed novel modulatory sites and mechanisms of action that are providing insights into the pathophysiology of certain anxiety disorders, potentially bridging the gap between the GABAergic and serotonergic circuits underlying anxiety. However, translating the pharmacological activity of compounds targeted to specific receptor subtypes in rodent models of anxiety to effective therapeutics in human anxiety has not been entirely successful. Since modulating any one of several broad classes of receptor targets can produce anxiolysis, we posit that a systems-level discovery platform combined with an individualized medicine approach based on noninvasive brain imaging would substantially advance the development of more effective therapeutics.

Footnotes

  • dx.doi.org/10.1124/pr.114.009126.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Pharmacological Reviews: 66 (4)
Pharmacological Reviews
Vol. 66, Issue 4
1 Oct 2014
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Review ArticleReview Article

Targeted Modulation of Neural Circuits Implicated in Anxiolysis

David H. Farb and Marcia H. Ratner
Pharmacological Reviews October 1, 2014, 66 (4) 1002-1032; DOI: https://doi.org/10.1124/pr.114.009126

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Review ArticleReview Article

Targeted Modulation of Neural Circuits Implicated in Anxiolysis

David H. Farb and Marcia H. Ratner
Pharmacological Reviews October 1, 2014, 66 (4) 1002-1032; DOI: https://doi.org/10.1124/pr.114.009126
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  • Article
    • Abstract
    • I. Introduction
    • II. Types of Anxiety Disorders
    • III. Brain-Imaging Studies: Assessment of Brain Activation in Patients with Anxiety Disorders
    • IV. Neural Systems and the Neurochemical Basis of Anxiety
    • V. Neuropsychopharmacology of Anxiety Disorders
    • VI. Conclusions
    • Acknowledgements
    • Authorship Contributions
    • Footnotes
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