Objetivo
"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."
Ámbito científico
Tema(s)
Convocatoria de propuestas
FP7-PEOPLE-2011-IEF
Consulte otros proyectos de esta convocatoria
Régimen de financiación
MC-IEF - Intra-European Fellowships (IEF)Coordinador
OX1 2JD Oxford
Reino Unido