Utilize este identificador para referenciar este registo:
https://hdl.handle.net/1822/61995
Título: | Serotonin 2C receptor antagonists induce fast-onset antidepressant effects |
Autor(es): | Opal, M. D. Klenotich, S. C. Morais, M. Bessa, J. Winkle, J. Doukas, D. Kay, L. J. Sousa, Nuno Dulawa, S. M. |
Palavras-chave: | Animals Antidepressive Agents Brain-Derived Neurotrophic Factor Chronic Disease Citalopram Cyclic AMP Response Element-Binding Protein Depressive Disorder Disease Models, Animal Elongation Factor 2 Kinase Female Mice, Inbred BALB C Olfactory Bulb Prefrontal Cortex Pyramidal Cells Receptor, Serotonin, 5-HT2C Receptors, Dopamine D1 Serotonin 5-HT2 Receptor Antagonists Serotonin Uptake Inhibitors Stress, Psychological TOR Serine-Threonine Kinases Time Factors eEF mTOR Neuronal remodeling antidepressant BDNF |
Data: | Out-2014 |
Editora: | Springer |
Revista: | Molecular Psychiatry |
Resumo(s): | Current antidepressants must be administered for several weeks to produce therapeutic effects. We show that selective serotonin 2C (5-HT2C) antagonists exert antidepressant actions with a faster-onset (5 days) than that of current antidepressants (14 days) in mice. Subchronic (5 days) treatment with 5-HT2C antagonists induced antidepressant behavioral effects in the chronic forced swim test (cFST), chronic mild stress (CMS) paradigm and olfactory bulbectomy paradigm. This treatment regimen also induced classical markers of antidepressant action: activation of cAMP response element-binding protein (CREB) and induction of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). None of these effects were induced by subchronic treatment with citalopram, a prototypical selective serotonin reuptake inhibitor (SSRI). Local infusion of 5-HT2C antagonists into the ventral tegmental area was sufficient to induce BDNF in the mPFC, and dopamine D1 receptor antagonist treatment blocked the antidepressant behavioral effects of 5-HT2C antagonists. 5-HT2C antagonists also activated mammalian target of rapamycin (mTOR) and eukaryotic elongation factor 2 (eEF2) in the mPFC, effects recently linked to rapid antidepressant action. Furthermore, 5-HT2C antagonists reversed CMS-induced atrophy of mPFC pyramidal neurons. Subchronic SSRI treatment, which does not induce antidepressant behavioral effects, also activated mTOR and eEF2 and reversed CMS-induced neuronal atrophy, indicating that these effects are not sufficient for antidepressant onset. Our findings reveal that 5-HT2C antagonists are putative fast-onset antidepressants, which act through enhancement of mesocortical dopaminergic signaling. |
Tipo: | Artigo |
URI: | https://hdl.handle.net/1822/61995 |
DOI: | 10.1038/mp.2013.144 |
ISSN: | 1359-4184 |
e-ISSN: | 1476-5578 |
Arbitragem científica: | yes |
Acesso: | Acesso restrito UMinho |
Aparece nas coleções: | ICVS - Artigos em revistas internacionais / Papers in international journals |
Ficheiros deste registo:
Ficheiro | Descrição | Tamanho | Formato | |
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Opal-2014-Serotonin-c-receptor-antagonists-in.pdf Acesso restrito! | 520,85 kB | Adobe PDF | Ver/Abrir |