Cited by 192Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchStress Responses and Cortisol

Serotonin-1A Autoreceptors Are Necessary and Sufficient for the Normal Formation of Circuits Underlying Innate Anxiety

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Richardson-Jones, Jesse W., Craige, Caryne P., Nguyen, Thanh H., Kung, Hank F., Gardier, Alain M., Dranovsky, Alex, David, Denis J., Guiard, Bruno P. +3 more·2011·The Journal of Neuroscience

Abstract

Identifying the factors contributing to the etiology of anxiety and depression is critical for the development of more efficacious therapies. Serotonin (5-HT) is intimately linked to both disorders. The inhibitory serotonin-1A (5-HT 1A) receptor exists in two separate populations with distinct effects on serotonergic signaling: (1) an autoreceptor that limits 5-HT release throughout the brain and (2) a heteroreceptor that mediates inhibitory responses to released 5-HT. Traditional pharmacologic and transgenic strategies have not addressed the distinct roles of these two receptor populations. Here we use a recently developed genetic mouse system to independently manipulate 5-HT 1A autoreceptor and heteroreceptor populations. We show that 5-HT 1A autoreceptors act to affect anxiety-like behavior. In contrast, 5-HT 1A heteroreceptors affect responses to forced swim stress, without effects on anxiety-like behavior. Together with our previously reported work, these results establish distinct roles for the two receptor populations, providing evidence that signaling through endogenous 5-HT 1A autoreceptors is necessary and sufficient for the establishment of normal anxiety-like behavior.

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Crossref · 10.1523/jneurosci.5836-10.2011

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  • Mouse studies show that greater expression of serotonin 1A autoreceptors produces less serotonin neuron firing and release and giving-up behavior in the tail suspension and forced swim tests.

    “Mouse studies show that greater expression of these autoreceptors produces a biological phenotype of less serotonin neuron firing and release and a behavioral phenotype manifesting giving-up behavior in the tail suspension test and the forced swim test (113).”

    From A brain-centric model of suicidal behavior (2020) · cites this paper as [113]

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Authors
Richardson-Jones, J. W., Craige, C. P., Nguyen, T. H., Kung, H. F., Gardier, A. M., Dranovsky, A., David, D. J., Guiard, B. P., Beck, S. G., Hen, R., & Leonardo, E. D.
Affiliations
  • Columbia University (US)
  • Children's Hospital of Philadelphia (US)
  • Université Paris-Sud (FR)
  • University of Pennsylvania (US)
  • New York State Psychiatric Institute (US)
Venue
The Journal of Neuroscience
Published
2011-04-20
Volume
31
Issue
16
Pages
6008-6018
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1996694057
Cited by
192
References
69
Citations by year
2026: 5 · 2025: 6 · 2024: 5 · 2023: 3 · 2022: 8 · 2021: 14 · 2020: 12 · 2019: 15 · 2018: 10 · 2017: 14 · 2016: 11 · 2015: 16 · 2014: 23 · 2013: 25 · 2012: 19
FWCI
9.67
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • AstraZeneca (CU08-8439)
  • National Alliance for Research on Schizophrenia and Depression
  • National Institutes of Health
  • National Institute of Mental Health (R01MH091844, R01MH075047, K08MH076083, R01MH091427, RC1MH089800, P01MH048125, R21MH099488, R01MH081968, K08MH079088, R01MH068542)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
5-HT1A receptor, 5-HT1A autoreceptors, anxiety-like behavior, forced swim stress, serotonergic signaling, serotonin release, depression, genetic mouse models
MeSH terms
Animals, Anxiety, Autoradiography, Behavior, Animal, Catalepsy, Electrophysiology, Nerve Net, Neurons, Microdialysis, Mice, Knockout, Receptor, Serotonin, 5-HT1A, Mice

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