Anxiety disorders and GABA neurotransmission: a disturbance of modulation

Philippe Nuss1,21Department of Psychiatry, Hôpital St Antoine, AP-HP, 2UMR 7203, INSERM ERL 1057 – Bioactive Molecules Laboratory, Pierre and Marie Curie University, Paris, FranceAbstract: Lines of evidence coming from many branches of neuroscience indicate that anxiety disorder...

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Autor principal:	Nuss P
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/5de6aded5b584656a8a876f416b70aee
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spelling	oai:doaj.org-article:5de6aded5b584656a8a876f416b70aee2021-12-02T04:54:24ZAnxiety disorders and GABA neurotransmission: a disturbance of modulation1178-2021https://doaj.org/article/5de6aded5b584656a8a876f416b70aee2015-01-01T00:00:00Zhttp://www.dovepress.com/anxiety-disorders-and-gaba-neurotransmission-a-disturbance-of-modulati-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021 Philippe Nuss1,21Department of Psychiatry, Hôpital St Antoine, AP-HP, 2UMR 7203, INSERM ERL 1057 – Bioactive Molecules Laboratory, Pierre and Marie Curie University, Paris, FranceAbstract: Lines of evidence coming from many branches of neuroscience indicate that anxiety disorders arise from a dysfunction in the modulation of brain circuits which regulate emotional responses to potentially threatening stimuli. The concept of anxiety disorders as a disturbance of emotional response regulation is a useful one as it allows anxiety to be explained in terms of a more general model of aberrant salience and also because it identifies avenues for developing psychological, behavioral, and pharmacological strategies for the treatment of anxiety disorder. These circuits involve bottom-up activity from the amygdala, indicating the presence of potentially threatening stimuli, and top-down control mechanisms originating in the prefrontal cortex, signaling the emotional salience of stimuli. Understanding the factors that control cortical mechanisms may open the way to identification of more effective cognitive behavioral strategies for managing anxiety disorders. The brain circuits in the amygdala are thought to comprise inhibitory networks of Υ-aminobutyric acid-ergic (GABAergic) interneurons and this neurotransmitter thus plays a key role in the modulation of anxiety responses both in the normal and pathological state. The presence of allosteric sites on the GABAA receptor allows the level of inhibition of neurons in the amygdala to be regulated with exquisite precision, and these sites are the molecular targets of the principal classes of anxiolytic drugs. Changes in the levels of endogenous modulators of these allosteric sites as well as changes in the subunit composition of the GABAA receptor may represent mechanisms whereby the level of neuronal inhibition is downregulated in pathological anxiety states. Neurosteroids are synthesized in the brain and act as allosteric modulators of the GABAA receptor. Since their synthesis is itself regulated by stress and by anxiogenic stimuli, targeting the neurosteroid-GABAA receptor axis represents an attractive target for the modulation of anxiety.Keywords: allosteric modulation, amygdala, salience, Υ-aminobutyric acid, neurosteroidsNuss PDove Medical PressarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2015, Iss default, Pp 165-175 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Nuss P Anxiety disorders and GABA neurotransmission: a disturbance of modulation
description	Philippe Nuss1,21Department of Psychiatry, Hôpital St Antoine, AP-HP, 2UMR 7203, INSERM ERL 1057 – Bioactive Molecules Laboratory, Pierre and Marie Curie University, Paris, FranceAbstract: Lines of evidence coming from many branches of neuroscience indicate that anxiety disorders arise from a dysfunction in the modulation of brain circuits which regulate emotional responses to potentially threatening stimuli. The concept of anxiety disorders as a disturbance of emotional response regulation is a useful one as it allows anxiety to be explained in terms of a more general model of aberrant salience and also because it identifies avenues for developing psychological, behavioral, and pharmacological strategies for the treatment of anxiety disorder. These circuits involve bottom-up activity from the amygdala, indicating the presence of potentially threatening stimuli, and top-down control mechanisms originating in the prefrontal cortex, signaling the emotional salience of stimuli. Understanding the factors that control cortical mechanisms may open the way to identification of more effective cognitive behavioral strategies for managing anxiety disorders. The brain circuits in the amygdala are thought to comprise inhibitory networks of Υ-aminobutyric acid-ergic (GABAergic) interneurons and this neurotransmitter thus plays a key role in the modulation of anxiety responses both in the normal and pathological state. The presence of allosteric sites on the GABAA receptor allows the level of inhibition of neurons in the amygdala to be regulated with exquisite precision, and these sites are the molecular targets of the principal classes of anxiolytic drugs. Changes in the levels of endogenous modulators of these allosteric sites as well as changes in the subunit composition of the GABAA receptor may represent mechanisms whereby the level of neuronal inhibition is downregulated in pathological anxiety states. Neurosteroids are synthesized in the brain and act as allosteric modulators of the GABAA receptor. Since their synthesis is itself regulated by stress and by anxiogenic stimuli, targeting the neurosteroid-GABAA receptor axis represents an attractive target for the modulation of anxiety.Keywords: allosteric modulation, amygdala, salience, Υ-aminobutyric acid, neurosteroids
format	article
author	Nuss P
author_facet	Nuss P
author_sort	Nuss P
title	Anxiety disorders and GABA neurotransmission: a disturbance of modulation
title_short	Anxiety disorders and GABA neurotransmission: a disturbance of modulation
title_full	Anxiety disorders and GABA neurotransmission: a disturbance of modulation
title_fullStr	Anxiety disorders and GABA neurotransmission: a disturbance of modulation
title_full_unstemmed	Anxiety disorders and GABA neurotransmission: a disturbance of modulation
title_sort	anxiety disorders and gaba neurotransmission: a disturbance of modulation
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/5de6aded5b584656a8a876f416b70aee
work_keys_str_mv	AT nussp anxietydisordersandgabaneurotransmissionadisturbanceofmodulation
_version_	1718401007130509312

Anxiety disorders and GABA neurotransmission: a disturbance of modulation

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