Ildefonso Hervs Andreu Raurich Luz Romero Roser Corts and Francesc Artigas

The term 'SSRIs' encompasses several chemical agents that have in common their ability to inhibit selectively the function of the serotonin (5-hydroxytryptamine, 5-HT) transporter. This is located on the membranes of serotonergic and glial cells of the brain and other cells outside the central nervous system (CNS), such as platelets, enterochromaffin cells of the gut, endothelial cells and mastocytes. The 5-HT transporter was cloned in 1991 from different cellular sources.1,2 It belongs to the same family as dopamine or noradrenaline transporters and is characterized by the presence of 12 transmembrane domains and intracellular N- and C-terminals.3 The cloned transporter displays the same pharmacological profile as the native protein expressed in brain preparations4-6 (e.g., synaptosomes or brain slices) and was soon recognized as sharing the identity of the CNS and peripheral 5-HT transporter in humans.7,8

By virtue of their ability to interfere with the process of internalization of 5-HT molecules via the 5-HT transporter, the SSRIs enhance the ratio of the concentrations of the extra-and intracellular compartments of 5-HT. Work using in vitro techniques to measure 5-HT uptake in brain preparations (e.g., brain slices or synaptosomes) and ex vivo neurochemical models led to the conclusion that SSRIs enhance serotonergic transmission by increasing the concentration of the transmitter in the interstitial brain space. However, work carried out in vivo, using single-unit recording in the dorsal raphé nucleus (DRN) and in vivo microdialysis, has provided a more complex view of the actions of SSRIs in brain.9 This chapter will summarize this evidence and will also focus on new therapeutic strategies based on these observations.

Defeat Depression

Defeat Depression

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