Academic Journal
5-HT2C receptor desensitization moderates anxiety in 5-HTT deficient mice: From behavioral to cellular evidence
| العنوان: | 5-HT2C receptor desensitization moderates anxiety in 5-HTT deficient mice: From behavioral to cellular evidence |
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| المؤلفون: | Martin, Cédric B. P., Martin, Vincent S., Trigo, JoséM., Chevarin, Caroline, Maldonado, Rafael, Fink, Latham L., Cunningham, Kathryn A., Hamon, Michel, Lanfumey, Laurence, Mongeau, Raymond |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2014 |
| المجموعة: | HighWire Press (Stanford University) |
| مصطلحات موضوعية: | Regular Research Article |
| الوصف: | Background: Desensitization and blockade of 5-HT 2C receptors (5-HT 2C R) have long been thought to be central in the therapeutic action of antidepressant drugs. However, besides behavioral pharmacology studies, there is little in vivo data documenting antidepressant-induced 5-HT 2C R desensitization in specific brain areas. Methods: Mice lacking the 5-HT reuptake carrier (5-HTT-/-) were used to model the consequences of chronic 5-HT reuptake inhibition with antidepressant drugs. The effect of this mutation on 5-HT 2C R was evaluated at the behavioral (social interaction, novelty-suppressed feeding and 5-HT 2C R-induced hypolocomotion tests), the neurochemical and the cellular (RT-qPCR, mRNA editing and c-fos-induced expression) levels. Results: Although 5-HTT-/- mice had an anxiogenic profile in the novelty-suppressed feeding test, they displayed less 5-HT 2C R-mediated anxiety in response to the agonist m-chlorophenylpiperazine in the social interaction test. In addition, 5-HT 2C R-mediated inhibition of stress-induced increase in 5-HT turnover, measured in various brain areas, was markedly reduced in 5-HTT-/- mutants. These indices of tolerance to 5-HT 2C R stimulation were associated neither with altered levels of 5-HT 2C R protein and mRNA nor with changes in pre-mRNA editing in the frontal cortex. However, basal c-fos mRNA production in cells expressing 5-HT 2C R was higher in 5-HTT-/- mutants, suggesting an altered basal activity of these cells following sustained 5-HT reuptake carrier inactivation. Furthermore, the increased c-fos mRNA expression in 5-HT 2C R-like immune-positive cortical cells observed in wild-type mice treated acutely with the 5-HT 2C R agonist RO-60,0175, was absent in 5-HTT-/- mutants. Conclusions: Such blunted responsiveness of the 5-HT 2C R system, observed at the cell signaling level, probably contributes to moderate the anxiety phenotype of 5-HTT-/- mice. |
| نوع الوثيقة: | text |
| وصف الملف: | text/html |
| اللغة: | English |
| Relation: | http://ijnp.oxfordjournals.org/cgi/content/short/pyu056v1; http://dx.doi.org/10.1093/ijnp/pyu056 |
| DOI: | 10.1093/ijnp/pyu056 |
| الاتاحة: | http://ijnp.oxfordjournals.org/cgi/content/short/pyu056v1 https://doi.org/10.1093/ijnp/pyu056 |
| Rights: | Copyright (C) 2014, Collegium Internationale Neuro-Psychopharmacologicum |
| رقم الانضمام: | edsbas.5858D85 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/ijnp/pyu056 |
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