Systemic enhancement of serotonin signaling reverses social deficits in multiple mouse models for ASD
Open accessAbstract
Autism spectrum disorder (ASD) is a common set of heterogeneous neurodevelopmental disorders resulting from a variety of genetic and environmental risk factors. A core feature of ASD is impairment in prosocial interactions. Current treatment options for individuals diagnosed with ASD are limited, with no current FDA-approved medications that effectively treat its core symptoms. We recently demonstrated that enhanced serotonin (5-HT) activity in the nucleus accumbens (NAc), via optogenetic activation of 5-HTergic inputs or direct infusion of a specific 5-HT1b receptor agonist, reverses social deficits in a genetic mouse model for ASD based on 16p11.2 copy number variation. Furthermore, the recreational drug MDMA, which is currently being evaluated in clinical trials, promotes sociability in mice due to its 5-HT releasing properties in the NAc. Here, we systematically evaluated the ability of MDMA and a selective 5-HT1b receptor agonist to rescue sociability deficits in multiple different mouse models for ASD. We find that MDMA administration enhances sociability in control mice and reverses sociability deficits in all four ASD mouse models examined, whereas administration of a 5-HT1b receptor agonist selectively rescued the sociability deficits in all six mouse models for ASD. These preclinical findings suggest that pharmacological enhancement of 5-HT release or direct 5-HT1b receptor activation may be therapeutically efficacious in ameliorating some of the core sociability deficits present across etiologically distinct presentations of ASD.
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MDMA ameliorated sociability deficits in four different mouse models for ASD.
“MDMA ameliorated sociability deficits in four different mouse models for ASD [124].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [124]
Administration of a specific 5-HT1b receptor agonist rescued sociability deficits in six different mouse models for ASD.
“administration of a specific 5-HT1b receptor agonist rescued sociability deficits in six different mouse models for ASD [124].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [124]
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Panzini, C. M., Ehlinger, D. G., Alchahin, A. M., Guo, Y., & Commons, K. G. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14227 · Cited by 20 · see citing works
Sensitization to the Prosocial Effects of 3,4-Methylenedioxymethamphetamine (MDMA)
Curry, D. W., Berro, L. F., Belkoff, A. R., Sulima, A., Rice, K. C., & Howell, L. L. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.03.017 · Cited by 13 · see citing works
Der-Ghazarian, T. S., Call, T., Scott, S. N., Dai, K., Brunwasser, S. J., Noudali, S. N., Pentkowski, N. S., & Neisewander, J. L. (2017) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2017.00073 · Cited by 12 · see citing works
Nasehi, M., Ghadimi, F., Khakpai, F., & Zarrindast, M. (2017) · Neuroscience Research · doi:10.1016/j.neures.2017.03.011 · Cited by 11 · see citing works
Editorial: Essential Pathways and Circuits of Autism Pathogenesis
Dölen, G., & Şahin, M. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00182 · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Anderson GM, Horne WC, Chatterjee D, Cohen DJ. The hyperserotonemia of autism. Ann N Y Acad Sci. 1990;600:331-40. discussion 41-2.
Cited by
Sorted by citations
Neural circuits regulating prosocial behaviors
Walsh, J. J., Christoffel, D. J., & Malenka, R. C. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-022-01348-8 · Cited by 72 · see citing works
Self-citation
- Authors
- Walsh, J. J., Llorach, P., Cardozo Pinto, D. F., Wenderski, W., Christoffel, D. J., Salgado, J. S., Heifets, B. D., Crabtree, G. R., & Malenka, R. C.
- Affiliations
- Stanford University (US)
- Stanford Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Malenka, Robert C.
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2021-07-08
- Volume
- 46
- Issue
- 11
- Pages
- 2000-2010
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC8429585
- OpenAlex
- W3179609913
- Cited by
- 56
- References
- 92
- Citations by year
- 2026: 8 · 2025: 18 · 2024: 10 · 2023: 10 · 2022: 8 · 2021: 2
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (Graduate Research Fellowship)
- Howard Hughes Medical Institute (Gilliam Fellowship)
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (F31 MH116588)
- U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (F99 NS118735, RO1 NS046789)
- Simons Foundation (SFARI 514863)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- autism spectrum disorder, serotonin signaling, 5-HT1B receptor agonist, MDMA, social dysfunction, nucleus accumbens, optogenetic stimulation, pharmacological rescue, social behavior
- MeSH terms
- Autism Spectrum Disorder, Animals, Disease Models, Animal, Serotonin, Social Behavior, Mice, DNA Copy Number Variations
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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