Serotonin, the periaqueductal gray and panic

Graeff, Frederico G

doi:10.1016/j.neubiorev.2003.12.004

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

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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The increased periaqueductal gray volume suggests differences in fear and panic responses between susceptible and resilient mice.
“pointing toward differences in fear and panic responses between susceptible and resilient mice (43,44,59).”
From Neuroanatomic differences associated with stress susceptibility and resilience (2016) · cites this paper as [59]

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Serotonin type II receptor activation facilitates synaptic plasticity via n-methyl-d-aspartate-mediated mechanism in the rat basolateral amygdala
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Dorsal raphe nucleus stimulation reduces centrally-elicited fearlike behavior
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Decreased left temporal lobe volume of panic patients measured by magnetic resonance imaging
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Brain correlates of an unexpected panic attack: a human positron emission tomographic study
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Dorsal periaqueductal gray punishment, septal lesions and the mode of action of minor tranquilizers
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Normative data for the personal report of confidence as a speaker
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Clomipramine, a better reference drug for panic/agoraphobia. I. Effectiveness comparison with imipramine
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Do panic patients process unconditioned fear vs. conditioned anxiety differently than normal subjects?
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Microinjection of propranolol into the dorsal periaqueductal gray causes an anxiolytic effect in the elevated plus-maze antagonized by ritanserin
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Ritanserin facilitates anxiety in a simulated public-speaking paradigm
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Enhancement of CO2-Induced Anxiety in Healthy Volunteers With the Serotonin Antagonist Metergoline
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Vulnerability and conditioning in relation to the human menstrual cycle
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D-fenfluramine selectively releases 5-HT from dorsal raphe terminals.
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The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner
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Neuropathic pain promotes adaptive changes in gene expression in brain networks involved in stress and depression
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Neurobiology of panic disorder: From animal models to brain neuroimaging
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Regional gray matter abnormalities in panic disorder: A voxel-based morphometry study
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A causal role for the anterior mid-cingulate cortex in negative affect and cognitive control
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Neural correlates of altered general emotion processing in social anxiety disorder
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Modulation of anxiety-like behaviour by Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels located in the dorsolateral periaqueductal gray
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Oxytocin receptor activity in the ventrocaudal periaqueductal gray modulates anxiety-related behavior in postpartum rats.
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Anxiolytic-like effects induced by blockade of transient receptor potential vanilloid type 1 (TRPV1) channels in the medial prefrontal cortex of rats
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Antipanic Efficacy of Paroxetine and Polymorphism within the Promoter of the Serotonin Transporter Gene
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Panic Disorder: Is the PAG Involved?
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The effects of intra-cerebral drug infusions on animals' unconditioned fear reactions: A systematic review
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Depression-Like Responses Induced by Daytime Light Deficiency in the Diurnal Grass Rat (Arvicanthis niloticus)
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Repeated social defeat increases reactive emotional coping behavior and alters functional responses in serotonergic neurons in the rat dorsal raphe nucleus
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Severe Serotonin Depletion after Conditional Deletion of the Vesicular Monoamine Transporter 2 Gene in Serotonin Neurons: Neural and Behavioral Consequences
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Respiratory regulation & interactions with neuro-cognitive circuitry
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The Deakin/Graeff hypothesis: Focus on serotonergic inhibition of panic
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Sight of conspecific images induces changes in neurochemistry in zebrafish
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5-HT2C Receptors in the Basolateral Amygdala and Dorsal Striatum Are a Novel Target for the Anxiolytic and Antidepressant Effects of Exercise
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Alterations in stress-associated behaviors and neurochemical markers in adult rats after neonatal short-lasting local inflammatory insult
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The basic neuroscience of emotional experiences in mammals: The case of subcortical FEAR circuitry and implications for clinical anxiety
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Values and Actions in Aversion
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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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