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Cited by 204Neurotransmitter Receptor Influence on BehaviorStress Responses and CortisolMemory and Neural Mechanisms

5-Hydroxytryptamine 2C Receptors in the Basolateral Amygdala Are Involved in the Expression of Anxiety After Uncontrollable Traumatic Stress

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Christianson, John P., Ragole, Thomas, Amat, Jose, Greenwood, Benjamin N., Strong, Paul V., Paul, Evan D., Fleshner, Monika, Watkins, Linda R. +1 more·2010·Biological Psychiatry
DOI 10.1016/j.biopsych.2009.09.011PMC PMC3278236
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Abstract

Background Exposure to uncontrollable stressors often increases anxiety-like behavior in both humans and rodents. In rat, this effect depends on stress-induced activity within the dorsal raphe nucleus (DRN). However, the role of serotonin in DRN projection regions is largely unknown. The goals of this study were to 1) assess the effect of uncontrollable stress on extracellular serotonin in the basolateral amygdala during the anxiety test, 2) determine whether DRN activity during a poststress anxiety test is involved in anxiety-like behavior, and 3) determine the role of the serotonin 2C receptor (5-HT(2C)) in uncontrollable stress-induced anxiety. Method Rats were exposed to tail shocks that were either controllable or uncontrollable. On the following day, anxiety-like behavior was assessed in a Juvenile Social Exploration (JSE) test. Basolateral amygdala (BLA) extracellular serotonin concentrations were assessed during JSE by in vivo microdialysis 24 hours after uncontrollable stress, controllable stress, or no stress. In separate experiments, drugs were administered before the JSE test to inhibit the DRN or to block 5-HT(2C) receptors. Results Exposure to uncontrollable shock reduced later social exploration. Prior uncontrollable stress potentiated serotonin efflux in the BLA during social exploration, but controllable stress did not. Intra-DRN 8-OH-DPAT and systemic and intra-BLA 5-HT(2C) receptor antagonist SB 242,084 prevented the expression of potentiated anxiety in uncontrollably stressed rats. Intra-BLA injection of the 5-HT(2C) agonist CP 809,101 mimicked the effect of stress. Conclusions These results suggest that the anxiety-like behavior observed after uncontrollable stress is mediated by exaggerated 5-HT acting at BLA 5-HT(2C) receptors.

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  • Microinjecting 5-HT2C antagonists into DRN target structures such as the amygdala during later testing blocked the passivity and increased anxiety that normally follow inescapable shock.

    “Indeed, microinjection of 5-HT2C antagonists directly into these structures does block the passivity and increased anxiety (Christianson et al., 2010; Strong et al., 2011).”

    From Learned helplessness at fifty: Insights from neuroscience. (2016) · cites this paper as Christianson et al., 2010

    The Results (Intra-BLA 5-HT2C receptor antagonism; page unavailable) report that microinjecting the antagonist into the basolateral amygdala before testing reversed the anxiety-like reduction in social exploration after inescapable shock. The Discussion says that whether the basolateral amygdala is involved in the antagonist’s effect on shuttle-box escape deficits remains to be determined. This paper therefore does not support the claim that microinjection blocked passivity. (LLM, conf=0.90)

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  • The mere presence of a juvenile leads to a large increase in 5-HT within the amygdala in a subject that has experienced inescapable shock, but not escapable shock previously.

    “However, the mere presence of a juvenile leads to a large increase in 5-HT within the amygdala in a subject that has experienced inescapable shock, but not escapable shock previously”

    From Learned helplessness at fifty: Insights from neuroscience. (2016) · cites this paper as Christianson et al., 2010

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Cited by

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Authors
Christianson, J. P., Ragole, T., Amat, J., Greenwood, B. N., Strong, P. V., Paul, E. D., Fleshner, M., Watkins, L. R., & Maier, S. F.
Affiliations
University of Colorado Boulder (US)
Corresponding author
Christianson, John P.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2010-02
Volume
67
Issue
4
Pages
339-345
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2009.09.011
PMC
PMC3278236
OpenAlex
W1999616055
Cited by
204
References
6
Citations by year
2026: 4 · 2025: 1 · 2024: 9 · 2023: 10 · 2022: 2 · 2021: 7 · 2020: 10 · 2019: 16 · 2018: 14 · 2017: 15 · 2016: 16 · 2015: 10 · 2014: 16 · 2013: 20 · 2012: 23
FWCI
6.92
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health (MH050479, MH082453)
  • University of Colorado Undergraduate Research Opportunities Program
  • Irene and Eric Simon Brain Research Foundation
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
5-HT2C receptor, serotonin, basolateral amygdala, dorsal raphe nucleus, uncontrollable stress, traumatic stress, anxiety-like behavior, social exploration, tail shock, extracellular serotonin, 8-OH-DPAT, microdialysis
MeSH terms
Aminopyridines, Amygdala, Analysis of Variance, Animals, Animals, Newborn, Anxiety, Disease Models, Animal, Electroshock, Indoles, Serotonin, Serotonin Antagonists, Social Behavior, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, Microdialysis, Stress Disorders, Traumatic, Receptor, Serotonin, 5-HT2C, Rats

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