Serotonin-1A Autoreceptors Are Necessary and Sufficient for the Normal Formation of Circuits Underlying Innate Anxiety
Open accessAbstract
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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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)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-04-20
- Volume
- 31
- Issue
- 16
- Pages
- 6008-6018
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3102496
- OpenAlex
- W1996694057
- Cited by
- 192
- References
- 69
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- FWCI
- 9.67
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- journal article
- Language
- en
- Open access
- hybrid
- doi.org
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- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
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- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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