Academic Journal
Sex differences in the antidepressant-like response and molecular events induced by the imidazoline-2 receptor agonist CR4056 in rats
| العنوان: | Sex differences in the antidepressant-like response and molecular events induced by the imidazoline-2 receptor agonist CR4056 in rats |
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| المؤلفون: | Hernández Hernández, Elena, Ledesma-Corvi, S., Yáñez-Gómez, Fernando, Garau, C., Gálvez-Melero, Laura, Bagán, Andrea, Escolano, Carmen, García-Fuster, M. Julia |
| المساهمون: | Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Govern de les Illes Balears, European Commission, Ministerio de Universidades (España), Universidad de Las Islas Baleares |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2023 |
| المجموعة: | Digital.CSIC (Consejo Superior de Investigaciones Científicas / Spanish National Research Council) |
| مصطلحات موضوعية: | I2 ligands Sex differences Depression Hippocampus Neurogenesis Rat |
| الوصف: | In searching for novel targets to design antidepressants, among the characterized imidazoline receptors (IR), I2 receptors are an innovative therapeutical approach since they are dysregulated in major depressive disorder and by classical antidepressant treatments. In fact, several I2 agonists have been characterized for their antidepressant-like potential, but the results in terms of efficacy were mixed and exclusively reported in male rodents. Since there are well-known sex differences in antidepressant-like efficacy, this study characterized the potential effects induced by two I2 drugs, CR4056 (i.e., most promising drug already in phase II clinical trial for its analgesic properties) and B06 (a compound from a new family of bicyclic α-iminophosphonates) under the stress of the forced-swim test in male and female rats exposed to early-life stress. Moreover, some hippocampal neuroplasticity markers related to the potential effects observed were also evaluated (i.e., FADD, p-ERK/ERK, mBDNF, cell proliferation: Ki-67 + cells). The main results replicated the only prior study reporting the efficacy of CR4056 in male rats, while providing new data on its efficacy in females, which was clearly dependent on prior early-life stress exposure. Moreover, B06 showed no antidepressant-like effects in male or female rats. Finally, CR4056 increased FADD content and decreased cell proliferation in hippocampus, without affecting p-ERK/t-ERK ratio and/or mBDNF content. Interestingly, these effects were exclusively observed in female rats, and independently of early-life conditions, suggesting some distinctive molecular underpinnings participating in the therapeutic response of CR4056 for both sexes. In conjunction, these results present CR4056 with an antidepressant-like potential, especially in female rats exposed to stress early in life, together with some neuronal correlates described in the context of these behavioral changes in females. ; This research was partly supported by several grants to MJG-F: PID2020-118582RB-I00 ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 1873-5177 |
| Relation: | #PLACEHOLDER_PARENT_METADATA_VALUE#; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-118582RB-I00/ES/NUEVAS OPCIONES TERAPEUTICAS PARA LA DEPRESION EN LA ADOLESCENCIA: EVALUACION PRECLINICA CON UNA PERSPECTIVA DE SEXO/; info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107991RB-I00/ES/REACCIONES MULTICOMPONENTE: DESCUBRIMIENTO, DEASARROLLO Y APLICACIONES EN BIOMEDICINA/; info:eu-repo/grantAgreement/AEI//PDC2022-133441- I00; Publisher's version; http://dx.doi.org/10.1016/j.pbb.2023.173527; Sí; Pharmacology Biochemistry and Behavior 223 (2023); http://hdl.handle.net/10261/310336 |
| DOI: | 10.1016/j.pbb.2023.173527 |
| الاتاحة: | http://hdl.handle.net/10261/310336 https://doi.org/10.1016/j.pbb.2023.173527 |
| Rights: | open |
| رقم الانضمام: | edsbas.A884AF6F |
| قاعدة البيانات: | BASE |
| تدمد: | 18735177 |
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| DOI: | 10.1016/j.pbb.2023.173527 |