Cited by 285Neurotransmitter Receptor Influence on BehaviorAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesMemory and Neural Mechanisms

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Serotonin, the periaqueductal gray and panic

Graeff, Frederico G·2004·Neuroscience & Biobehavioral Reviews

DOI 10.1016/j.neubiorev.2003.12.004

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Abstract

This article reviews experimental evidence and theoretical constructs that implicate serotonin (5-HT) modulation of defensive behavior within the midbrain periaqueductal gray in panic disorder (PD). Evidence with conflict tests in experimental animals indicates that 5-HT enhances anxiety, whereas results with aversive stimulation of the dorsal periaqueductal gray point to an anxiolytic role of 5-HT. To solve this contradiction, it has been suggested that the emotional states determined by the two types of animal model are different. Conflict tests would generate conditioned anxiety, whereas periaqueductal gray stimulation would produce unconditioned fear, as evoked by proximal threat. Clinically, the former would be related to generalized anxiety while the latter to PD. Thus, 5-HT is supposed to facilitate anxiety, but to inhibit panic. This hypothesis has been tested in the animal model of anxiety and panic named the elevated T-maze, in two procedures of human experimental anxiety applied to healthy volunteers or panic patients, and in CO2-induced panic attacks. Overall, the obtained results have shown that drugs that enhance 5-HT function increase different indexes of anxiety, but decrease indexes of panic. Drugs that impair 5-HT function have the opposite effects. Thus, so far the predictions derived from the above hypothesis have been fulfilled.

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Authors: Graeff, F. G.
Affiliations: Universidade de São Paulo (BR)
Corresponding author: Graeff, Frederico G
ORCID: Graeff, Frederico G
Venue: Neuroscience & Biobehavioral Reviews
Publisher: Elsevier BV
Published: 2004-05
Volume: 28
Issue: 3
Pages: 239-259
ISSN: 0149-7634 (ISSN-L)
DOI: 10.1016/j.neubiorev.2003.12.004
OpenAlex: W2143184913
Cited by: 285
References: 144
Citations by year: 2026: 2 · 2025: 2 · 2024: 9 · 2023: 2 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 9 · 2018: 7 · 2017: 12 · 2016: 5 · 2015: 19 · 2014: 15 · 2013: 18 · 2012: 17
FWCI: 1.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience & Biobehavioral Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: serotonin, periaqueductal gray, panic disorder, defensive behavior, anxiety, elevated T-maze, conditioned anxiety, unconditioned fear, anxiolytic effects, generalized anxiety disorder
MeSH terms: Animals, Anxiety, Brain Mapping, Conflict, Psychological, Escape Reaction, Humans, Models, Psychological, Periaqueductal Gray, Serotonin, Panic Disorder

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Serotonin, the periaqueductal gray and panic

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