TIVMOAN5FP
Translational in vivo modelling of a novel 5-HT feedback pathway
| Coordinatore | THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Organization address
address: University Offices, Wellington Square contact info |
| Nazionalità Coordinatore | United Kingdom [UK] |
| Totale costo | 200˙371 € |
| EC contributo | 200˙371 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2011-IEF |
| Funding Scheme | MC-IEF |
| Anno di inizio | 0 |
| Periodo (anno-mese-giorno) | 0000-00-00 - 0000-00-00 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Organization address
address: University Offices, Wellington Square contact info |
UK (OXFORD) | coordinator | 200˙371.80 |
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Obiettivo del progetto (Objective)
'Despite the devastating impact of major depression on society, our knowledge of the brain mechanisms of depression is such that individuals at risk cannot be reliably detected, over a third of patients are refractory to treatment, and patients are being managed on a daily basis with antidepressant strategies without the guidance of a satisfactory explanation of their mechanisms of action. The neurotransmitter 5-hydroxytryptamine (5-HT, serotonin) is critically important for maintaining mood in vulnerable patients and the therapeutic effect of antidepressant drugs. Recent progress in understanding the role of 5-HT in the neurobiology of depression has led to a focus on 5-HT receptor subtypes, and particularly 5-HT2C receptors, and to the real possibility of resulting therapeutic advances. The present project seeks to provide critical, timely, and translationally-relevant information about a potential key player in the link between 5-HT2C receptors and depression, a 5-HT2C feedback pathway that our work has recently uncovered. In this proposal we aim to address key questions regarding the fundamental aspects of 5-HT2C feedback circuitry and its sensitivity to stress and antidepressant treatment, and expand our pilot animal imaging study of WAY 161503 with a rigorous pharmacological analysis of the BOLD changes in the LHb and DRN, including investigation of the effects of mCPP. We will compliment this animal imaging study with a recently described functional connectivity analysis35 focused on the LHb-DRN pathway. Finally, we will investigate the potential of using a mCPP challenge in combination with fMRI to model the 5-HT2C LHb-DRN feedback pathway in human volunteers. The work will thus contribute to a clinically important and rapidly evolving area of neuroscience.'