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

The DOI matches its Crossref record; 144 of the 144 references it cites were found in a registry or an index.

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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Citations

Cites

Research works printed but not linked: 10

  1. Andrade, 2000, Role of the median raphe nucleus in the modulation of two types of fear/anxiety responses in rats submitted to the elevated T-maze, J Psychopharmacol, 14, A38
  2. Freud, 1959, Inhibition, symptoms and anxiety, vol. 20
  3. Gentil, 1988, The aversive system, 5HT and panic attacks, vol. 1, 142
  4. Graeff, 1988, Animal models of aversion, vol. 1, 115
  5. Graeff, 1990, Brain defense systems and anxiety, vol. 3, 307
  6. Kennett, 1993, 5-HT1C receptors and their therapeutic relevance, Curr Opin Invest Drugs, 2, 317
  7. Leal, 2003, Simulated public speaking did not activate the hypothalamic-pituitary-adrenal axis in neither panic patients or healthy controls, J Psychopharmacol, 17, A24/A79
  8. Nashold, 1974, The midbrain and pain, vol. 4, 191
  9. Petersen, 1984, Anticonflict effects of 5-HT antagonists by intraamygdaloid injection, Abstr 14th CINP Cong, 654
  10. Vargas, 2001, Pharmacological and endocrinological properties of intracranially-induced panic-like behaviors, Soc Neurosci Abstr, 27, 858.11

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Metadata

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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