Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study

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• dc.contributor.author Pascual-Antón, Raquel
• dc.contributor.author Blasco-Serra, Arantxa
• dc.contributor.author Muñoz-Moreno, Emma
• dc.contributor.author Pilar-Cuéllar, Fuencisla
• dc.contributor.author Garro-Martínez, Emilio
• dc.contributor.author Florensa-Zanuy, Eva
• dc.contributor.author López-Gil, Xavier
• dc.contributor.author Campa, Víctor M.
• dc.contributor.author Soria Rodríguez, Guadalupe
• dc.contributor.author Adell, Albert
• dc.date.accessioned 2025-11-24T07:06:42Z
• dc.date.available 2025-11-24T07:06:42Z
• dc.date.issued 2021
• dc.description.abstract Ketamine has rapid and robust antidepressant effects. However, unwanted psychotomimetic effects limit its widespread use. Hence, several studies examined whether GluN2B-subunit selective NMDA antagonists would exhibit a better therapeutic profile. Although preclinical work has revealed some of the mechanisms of action of ketamine at cellular and molecular levels, the impact on brain circuitry is poorly understood. Several neuroimaging studies have examined the functional changes in the brain induced by acute administration of ketamine and Ro 25-6981 (a GluN2B-subunit selective antagonist), but the changes in the microstructure of gray and white matter have received less attention. Here, the effects of ketamine and Ro 25-6981 on gray and white matter integrity in male Sprague–Dawley rats were determined using diffusion-weighted magnetic resonance imaging (DWI). In addition, DWI-based structural brain networks were estimated and connectivity metrics were computed at the regional level. Immunohistochemical analyses were also performed to determine whether changes in myelin basic protein (MBP) and neurofilament heavy-chain protein (NF200) may underlie connectivity changes. In general, ketamine and Ro 25-6981 showed some opposite structural alterations, but both compounds coincided only in increasing the fractional anisotropy in infralimbic prefrontal cortex and dorsal raphe nucleus. These changes were associated with increments of NF200 in deep layers of the infralimbic cortex (together with increased MBP) and the dorsal raphe nucleus. Our results suggest that the synthesis of NF200 and MBP may contribute to the formation of new dendritic spines and myelination, respectively. We also suggest that the increase of fractional anisotropy of the infralimbic and dorsal raphe nucleus areas could represent a biomarker of a rapid antidepressant response.en
• dc.description.sponsorship Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants from the Instituto de Salud Carlos III, Subdirección General de Evaluación y Fomento de la Investigación (PI13/00038, PI16/00217 and PI19/00170 to A.A.) that were co-funded by the European Regional Development Fund (‘A way to build Europe’); Generalitat Valenciana, Conselleria d’ Educació, Investigació, Cultura i Esport (GV/2018/049 to A.B-S.); Ministerio de Ciencia, Innovación y Universidades (RTI2018-097534-B-I00 to F.P.-C.). Funding from the Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III is also acknowledged. The funding agencies had no role in the design and conduct of the study, collection, management, analyses, and interpretation of the data; and preparation, review, or approval of the manuscript and the decision to submit it for publication.en
• dc.format.mimetype application/pdf
• dc.identifier.citation Pascual-Antón R, Blasco-Serra A, Muñoz-Moreno E, Pilar-Cuéllar F, Garro-Martínez E, Florensa-Zanuy E, et al. Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling study. Brain Struct Funct. 2021;226(8):2603–16. DOI: 10.1007/s00429-021-02354-0
• dc.identifier.doi http://dx.doi.org/10.1007/s00429-021-02354-0
• dc.identifier.issn 1863-2661
• dc.identifier.uri http://hdl.handle.net/10230/71977
• dc.language.iso eng
• dc.publisher Springer
• dc.relation.ispartof Brain Structure and Function. 2021;226(8):2603–16
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/RTI2018-097534-B-I00
• dc.rights This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Neuroimagingen
• dc.subject.keyword Dorsal raphe nucleusen
• dc.subject.keyword Infralimbic cortexen
• dc.subject.keyword Fast-acting antidepressanten
• dc.subject.keyword Neurofilamenten
• dc.subject.keyword Myelinizationen
• dc.title Structural connectivity and subcellular changes after antidepressant doses of ketamine and Ro 25-6981 in the rat: an MRI and immuno-labeling studyen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion