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Rafael Moliner, Mykhailo Girych, Cecilia Anna Brunello, Vera D. Kovaleva, Caroline Biojone, Giray Enkavi, Lina Antenucci, Erik F. Kot, Sergey A. Goncharuk, Katja Kaurinkoski and 23 more
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.
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Moliner, R., Girych, M., Brunello, C. A., Kovaleva, V. D., 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. R., Seiffert, N., Rubiolo, A., Haapaniemi, H., … Ċastrén, E. (2023). Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nature Neuroscience, 26(6), 1032–1041. https://doi.org/10.1038/s41593-023-01316-5
Moliner, Rafael, et al. "Psychedelics promote plasticity by directly binding to BDNF receptor TrkB." Nature Neuroscience, vol. 26, no. 6, 2023, pp. 1032–1041, https://doi.org/10.1038/s41593-023-01316-5.
Moliner, Rafael, Mykhailo Girych, Cecilia Anna Brunello, Vera D. Kovaleva, Caroline Biojone, Giray Enkavi, Lina Antenucci, et al. "Psychedelics promote plasticity by directly binding to BDNF receptor TrkB." Nature Neuroscience 26, no. 6 (2023): 1032–1041. https://doi.org/10.1038/s41593-023-01316-5.
Moliner R., Girych M., Brunello C. A. [и др.] Psychedelics promote plasticity by directly binding to BDNF receptor TrkB // Nature Neuroscience. — 2023. — Vol. 26, № 6. — P. 1032–1041. — URL: https://doi.org/10.1038/s41593-023-01316-5
@article{moliner2023psychedelics,
title = {{Psychedelics promote plasticity by directly binding to BDNF receptor TrkB}},
author = {Rafael Moliner and Mykhailo Girych and Cecilia Anna Brunello and Vera D. 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 R.A.F. Diniz and Nina Seiffert and Anna Rubiolo and Hele Haapaniemi and Elsa Meshi and Elina I. Nagaeva and Tiina Öhman and Tomasz Róg and Esko M Kankuri and Marçal Vilar and Markku T Varjosalo and Esa R. Korpi and Perttu Permi and Konstantin S. Mineev and Märt Saarma and Ilpo Vattulainen and Plinio Cabrera Casarotto and Eero Ċastrén},
journal = {Nature Neuroscience},
year = {2023},
volume = {26},
number = {6},
pages = {1032--1041},
doi = {10.1038/s41593-023-01316-5},
url = {https://doi.org/10.1038/s41593-023-01316-5}
}TY - JOUR AU - Moliner, Rafael AU - Girych, Mykhailo AU - Brunello, Cecilia Anna AU - Kovaleva, Vera D. 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 R.A.F. AU - Seiffert, Nina AU - Rubiolo, Anna AU - Haapaniemi, Hele AU - Meshi, Elsa AU - Nagaeva, Elina I. AU - Öhman, Tiina AU - Róg, Tomasz AU - Kankuri, Esko M AU - Vilar, Marçal AU - Varjosalo, Markku T AU - Korpi, Esa R. AU - Permi, Perttu AU - Mineev, Konstantin S. AU - Saarma, Märt AU - Vattulainen, Ilpo AU - Casarotto, Plinio Cabrera AU - Ċastrén, Eero TI - Psychedelics promote plasticity by directly binding to BDNF receptor TrkB JO - Nature Neuroscience VL - 26 IS - 6 SP - 1032 EP - 1041 PY - 2023 DA - 2023/06/01 DO - 10.1038/s41593-023-01316-5 UR - https://doi.org/10.1038/s41593-023-01316-5 ER -
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