The majority of 5-HT fibres originate from the dorsal and median raphe nuclei: DRN and MRN repectively, where 5-HT1A, 5-HT1B, 5-HT1D, 5-HT5A and 5-HT7 receptors have been localised in the raphe. Selective receptor antagonists are available to investigate the function of these receptors, except for 5-HT5A where we still await the discovery of selective compounds.
In the DRN, 5-HT1A receptors play an important role in regulating 5-HT release. Both 5-HT1B and 5-HT7 receptor antagonists have little effect on 5-HT release per se but increase 5-HT release in the presence of 5-HT1A receptor blockade. In contrast, 5-HT1D receptor antagonists increase 5-HT release per se and are not affected by 5-HT1A receptor blockade. In the MRN, 5-HT1B receptors are thought to play a more dominant function in regulating 5-HT release. 5-HT1B receptor blockade increases 5-HT release per se which is not modulated by 5-HT1A receptor antagonism.
Therefore, to achieve maximum elevation of 5-HT release in the raphe nuclei one would need either a combination 5-HT1A and 5-HT1B or 5-HT1A and 5-HT7 receptor blockade. However, we await the emergence of selective 5-HT5A compounds to assess the functional importance of this receptor in the raphe.
Buy this Article