Nature Neuroscience

, volume 26 , issue 6 , pages 1032-1041

Psychedelics promote plasticity by directly binding to BDNF receptor TrkB

Rafael Moliner ^{1, 2}

Mykhailo Girych ³

Cecilia Brunello ¹

Vera Kovaleva ⁴

Caroline Biojone ^{1, 5, 6}

Giray Enkavi ³

Lina Antenucci ⁷

Erik F Kot ^{8, 9}

Sergey A. Goncharuk ^{8, 9}

Katja Kaurinkoski ¹

Mirjami Kuutti ¹

Senem Merve Fred ¹

Lauri V Elsilä ²

Sven Sakson ⁴

Cecilia Cannarozzo ¹

Cassiano Diniz ¹⁰

Nina Seiffert ¹

Anna Rubiolo ¹¹

Hele Haapaniemi ¹

Elsa Meshi ¹²

Elina Nagaeva ²

Tiina Öhman ⁴

Tomasz Róg ³

E. Kankuri ²

M. Vilar ¹³

M. Varjosalo ⁴

E. R. Korpi ²

Perttu Permi ^{7, 14, 15}

Konstantin S. Mineev ^{8, 9, 16}

Mart Saarma ⁴

Ilpo Vattulainen ³

Plinio C. Casarotto ¹

E. Castrén ¹

Hide authors affiliations Show authors affiliations: 16 affiliations

Neuroscience Center, HiLife, University of Helsinki, Helsinki, Finland |

Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland |

Department of Physics, Faculty of Science, University of Helsinki, Helsinki, Finland |

⁴

Institute of Biotechnology, Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland |

⁵

Department of Biomedicine, Faculty of Health, Aarhus University, Aarhus, Denmark |

⁶

Translational Neuropsychiatry Unit, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark |

⁷

Department of Chemistry, NanoScience Center, University of Jyväskylä, Jyväskylä, Finland |

⁸

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, RAS, Moscow, Russia |

⁹

Moscow Institute of Physics and Technology, Dolgoprudny, Russia |

¹⁰

Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil |

¹¹

Neuroscience, University of Trieste, Trieste, Italy |

¹²

Biomedical Sciences, Hellenic University of Thessaloniki, Thessaloniki, Greece |

¹³

Molecular Basis of Neurodegeneration Unit, Instituto de Biomedicina de Valencia, CSIC, Valencia, Spain |

¹⁴

Department of Biological and Environmental Science, Nanoscience center, University of Jyväskylä, Jyväskylä, Finland |

¹⁵

Structural and Quantitative Biology Research Program, Institute of Biotechnology, Instruct-HiLIFE, University of Helsinki, Helsinki, Finland |

¹⁶

Institute for Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Johann Wolfgang Goethe University, Frankfurt am Main, Germany |

Publication type: Journal Article

Publication date: 2023-06-05

Springer Nature

Nature Neuroscience

scimago Q1

wos Q1

SJR: 11.197

CiteScore: 35.4

Impact factor: 20.0

ISSN: 10976256, 15461726

DOI: 10.1038/s41593-023-01316-5

Copy DOI

PubMed ID: 37280397

General Neuroscience

Abstract

Psychedelics produce fast and persistent antidepressant effects and induce neuroplasticity resembling the effects of clinically approved antidepressants. We recently reported that pharmacologically diverse antidepressants, including fluoxetine and ketamine, act by binding to TrkB, the receptor for BDNF. Here we show that lysergic acid diethylamide (LSD) and psilocin directly bind to TrkB with affinities 1,000-fold higher than those for other antidepressants, and that psychedelics and antidepressants bind to distinct but partially overlapping sites within the transmembrane domain of TrkB dimers. The effects of psychedelics on neurotrophic signaling, plasticity and antidepressant-like behavior in mice depend on TrkB binding and promotion of endogenous BDNF signaling but are independent of serotonin 2A receptor (5-HT_2A) activation, whereas LSD-induced head twitching is dependent on 5-HT_2A and independent of TrkB binding. Our data confirm TrkB as a common primary target for antidepressants and suggest that high-affinity TrkB positive allosteric modulators lacking 5-HT_2A activity may retain the antidepressant potential of psychedelics without hallucinogenic effects.

Found

2 citations

Trindade Pablo

22 publications, 1 739 citations, 12 reviews

h-index: 12

Universidade Federal do Rio de Janeiro

1 citation

Biso Letizia

15 publications, 77 citations, 5 reviews

h-index: 6

University of Pisa

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GOST |

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GOST Copy

Moliner R. et al. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB // Nature Neuroscience. 2023. Vol. 26. No. 6. pp. 1032-1041.

GOST all authors (up to 50) Copy

Moliner R., Girych M., Brunello C., Kovaleva V., Biojone C., Enkavi G., Antenucci L., Kot E. F., Goncharuk S. A., Kaurinkoski K., Kuutti M., Fred S. M., Elsilä L. V., Sakson S., Cannarozzo C., Diniz C., Seiffert N., Rubiolo A., Haapaniemi H., Meshi E., Nagaeva E., Öhman T., Róg T., Kankuri E., Vilar M., Varjosalo M., Korpi E. R., Permi P., Mineev K., Saarma M., Vattulainen I., Casarotto P. C., Castrén E. Psychedelics promote plasticity by directly binding to BDNF receptor TrkB // Nature Neuroscience. 2023. Vol. 26. No. 6. pp. 1032-1041.

RIS |

Cite this

RIS Copy

TY - JOUR

DO - 10.1038/s41593-023-01316-5

UR - https://doi.org/10.1038/s41593-023-01316-5

TI - Psychedelics promote plasticity by directly binding to BDNF receptor TrkB

T2 - Nature Neuroscience

AU - Moliner, Rafael

AU - Girych, Mykhailo

AU - Brunello, Cecilia

AU - Kovaleva, Vera

AU - Biojone, Caroline

AU - Enkavi, Giray

AU - Antenucci, Lina

AU - Kot, Erik F

AU - Goncharuk, Sergey A.

AU - Kaurinkoski, Katja

AU - Kuutti, Mirjami

AU - Fred, Senem Merve

AU - Elsilä, Lauri V

AU - Sakson, Sven

AU - Cannarozzo, Cecilia

AU - Diniz, Cassiano

AU - Seiffert, Nina

AU - Rubiolo, Anna

AU - Haapaniemi, Hele

AU - Meshi, Elsa

AU - Nagaeva, Elina

AU - Öhman, Tiina

AU - Róg, Tomasz

AU - Kankuri, E.

AU - Vilar, M.

AU - Varjosalo, M.

AU - Korpi, E. R.

AU - Permi, Perttu

AU - Mineev, Konstantin S.

AU - Saarma, Mart

AU - Vattulainen, Ilpo

AU - Casarotto, Plinio C.

AU - Castrén, E.

PY - 2023

DA - 2023/06/05

PB - Springer Nature

SP - 1032-1041

IS - 6

VL - 26

PMID - 37280397

SN - 1097-6256

SN - 1546-1726

ER -

BibTex |

Cite this

BibTex (up to 50 authors) Copy

@article{2023_Moliner,

author = {Rafael Moliner and Mykhailo Girych and Cecilia Brunello and Vera Kovaleva and Caroline Biojone and Giray Enkavi and Lina Antenucci and Erik F Kot and Sergey A. Goncharuk and Katja Kaurinkoski and Mirjami Kuutti and Senem Merve Fred and Lauri V Elsilä and Sven Sakson and Cecilia Cannarozzo and Cassiano Diniz and Nina Seiffert and Anna Rubiolo and Hele Haapaniemi and Elsa Meshi and Elina Nagaeva and Tiina Öhman and Tomasz Róg and E. Kankuri and M. Vilar and M. Varjosalo and E. R. Korpi and Perttu Permi and Konstantin S. Mineev and Mart Saarma and Ilpo Vattulainen and Plinio C. Casarotto and E. Castrén},

title = {Psychedelics promote plasticity by directly binding to BDNF receptor TrkB},

journal = {Nature Neuroscience},

year = {2023},

volume = {26},

publisher = {Springer Nature},

month = {jun},

url = {https://doi.org/10.1038/s41593-023-01316-5},

number = {6},

pages = {1032--1041},

doi = {10.1038/s41593-023-01316-5}

}

MLA

Cite this

MLA Copy

Moliner, Rafael, et al. “Psychedelics promote plasticity by directly binding to BDNF receptor TrkB.” Nature Neuroscience, vol. 26, no. 6, Jun. 2023, pp. 1032-1041. https://doi.org/10.1038/s41593-023-01316-5.

Publisher

Springer Nature

Journal

Nature Neuroscience

scimago Q1

wos Q1

SJR

11.197

CiteScore

35.4

Impact factor

20.0

ISSN

10976256 (Print)

15461726 (Electronic)

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Из психоделиков сделали антидепрессант, убрав галлюциногенный эффект