Manipulation of dorsal raphe serotonergic neurons modulates active coping to inescapable stress and anxiety-related behaviors in mice and rats
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Major depression and anxiety disorders are a social and economic burden worldwide. Serotonergic signaling has been implicated in the pathophysiology of these disorders and thus has been a crucial target for pharmacotherapy. However, the precise mechanisms underlying these disorders are still unclear. Here, we used species-optimized lentiviral vectors that were capable of efficient and specific transduction of serotonergic neurons in mice and rats for elucidation of serotonergic roles in anxiety-like behaviors and active coping behavior in both species. Immunohistochemical analyses revealed that lentiviral vectors with an upstream sequence of tryptophan hydroxylase 2 gene efficiently transduced serotonergic neurons with a specificity of approximately 95% in both mice and rats. Electrophysiological recordings showed that these lentiviral vectors induced sufficient expression of optogenetic tools for precise control of serotonergic neurons. Using these vectors, we demonstrate that acute activation of serotonergic neurons in the dorsal raphe nucleus increases active coping with inescapable stress in rats and mice in a time-locked manner, and that acute inhibition of these neurons increases anxiety-like behaviors specifically in rats. These findings further our understanding of the pathophysiological role of dorsal raphe serotonergic neurons in different species and the role of these neurons as therapeutic targets in major depression and anxiety disorders.
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Acute activation of serotoninergic neurons in the DRN increases active coping to inescapable stress.
“recent evidence suggests that acute activation of serotoninergic neurons in the DRN increase active coping to inescapable stress (179)”
From Psychedelics and Other Psychoplastogens for Treating Mental Illness. (2021) · cites this paper as [179]
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- Authors
- Nishitani, N., Nagayasu, K., Asaoka, N., Yamashiro, M., Andoh, C., Nagai, Y., Kinoshita, H., Kawai, H., Shibui, N., Liu, B., Hewinson, J., Shirakawa, H., Nakagawa, T., Hashimoto, H., Kasparov, S., & Kaneko, S.
- Affiliations
- Kyoto University (JP)
- University of Bristol (GB)
- Kyoto University Hospital (JP)
- Kanazawa University (JP)
- Corresponding author
- Nagayasu, Kazuki
- Kasparov, Sergey
- Kaneko, Shuji
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2018-10-30
- Volume
- 44
- Issue
- 4
- Pages
- 721-732
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC6372597
- OpenAlex
- W2898931094
- Cited by
- 92
- References
- 52
- Citations by year
- 2026: 7 · 2025: 10 · 2024: 14 · 2023: 8 · 2022: 13 · 2021: 20 · 2020: 10 · 2019: 10
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuropsychopharmacology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Japan Agency for Medical Research and Development
- Jikei University School of Medicine
- Medical Research Council (MR/L020661/1)
- Biotechnology and Biological Sciences Research Council (MR/L020661/1, BB/L019396/1)
- Japan Society for the Promotion of Science (17H03989)
- RIKEN
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- dorsal raphe nucleus, serotonergic neurons, active coping, inescapable stress, anxiety-like behavior, major depressive disorder, anxiety disorders, tryptophan hydroxylase 2, lentiviral vectors, optogenetics, species differences, therapeutic target
- MeSH terms
- Adaptation, Psychological, Animals, Anxiety, Behavior, Animal, Disease Models, Animal, Genetic Vectors, Male, Mice, Inbred C57BL, Lentivirus, Rats, Wistar, Mice, Rats, Electrophysiological Phenomena, Serotonergic Neurons, Optogenetics, Dorsal Raphe Nucleus
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