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Chapter 6.3 The use of brain microdialysis in antidepressant drug research

Autor Artigas, Francesc ; Adell, Albert
Fecha de publicación 2006
Citación Handbook of Behavioral Neuroscience 16: 527-543 (2006)
ResumenThe appropriate treatment of depression is a major challenge in health policies, given the large prevalence of this psychiatric condition. Current antidepressant treatments have two main problems: slowness of action and limited efficacy. Ideally, antidepressants should exert most their clinical action in a relatively short time (e.g., 2 weeks) and be effective in the majority of treated patients. However, the most used antidepressants such as the selective serotonin reuptake inhibitors (SSRIs) induce a clinical response (reduction to half of the initial severity) in only 60% of the patients after 6 weeks of treatment. Microdialysis studies over the last 15 years have helped to determine that the limited action of antidepressant drugs is partly due to negative feedback mechanisms involving 5-HT autoreceptors. The activation of such receptors by the excess 5-HT in the extracellular brain space reduces serotonergic cell firing and 5-HT release, thus attenuating the increase produced by reuptake inhibition. Chronic antidepressant treatment results in a progressive desensitization of these negative feedback mechanisms, enabling 5-HT neurons to recover their firing and release activities. This process is thought to play an important role in the delayed therapeutic action of antidepressants. This chapter reviews the use of the microdialysis technique to study the mode of action of SSRIs and other marketed (noradrenaline reuptake inhibitors, serotonin, and noradrenaline reuptake inhibitors) or potential antidepressant drugs (NK1 and CRF antagonists). Overall, microdialysis has largely contributed to the current knowledge on the mode of action of antidepressant drugs and to the development of potential new therapeutic strategies in the field. © 2007 Elsevier B.V. All rights reserved.
Versión del editorhttp://dx.doi.org/10.1016/S1569-7339(06)16028-2
URI http://hdl.handle.net/10261/112766
Identificadoresdoi: 10.1016/S1569-7339(06)16028-2
issn: 1569-7339
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