Serotonin, a well-known neurotransmitter in mammals, has been linked to a number of neurological and gastrointestinal disorders. One of these disorders, serotonin syndrome, is a potentially deadly condition caused by increased levels of serotonin in the extracellular space. Information on the neurochemical effects of serotonin syndrome on serotonin catabolism is lacking, particularly in relation to the enteric system of the gastrointestinal tract. Here the catabolism of serotonin is monitored in rats with pharmacologically induced serotonin syndrome, with the catabolites characterized using a specialized capillary electrophoresis system with laser-induced native fluorescence detection. Animals induced with serotonin syndrome demonstrate striking increases in the levels of serotonin and its metabolites. In the brain, levels of serotonin increased 2-to 3-fold in animals induced with serotonin syndrome. A major serotonin metabolite, 5-hydroxyindole acetic acid, increased 10-to 100-fold in experimental animals. Similar results were observed in the gastrointestinal tissues; in the small intestines, serotonin levels increased 4-to 5-fold. Concentrations of 5-hydroxyindole acetic acid increased 32-to 100-fold in the intestinal tissues of experimental animals. Serotonin sulfate showed surprisingly large increases, marking what may be the first time the compound has been reported in rat intestinal tissues. Keywords: capillary electrophoresis system with laserinduced native fluorescence detection, enteric nervous system, serotonin, serotonin metabolism, serotonin sulfate, serotonin syndrome. Serotonin (5-HT) is well known as a neurotransmitter in the CNS of mammals where it plays an important role in learning and memory (Martin et al. 1997;Buhot et al. 2000) and in various stages of development (Gaspar et al. 2003). Imbalances in levels of 5-HT have been observed in a number of neurological disorders including: Parkinson, Huntington, Alzheimer, Alzheimer-like dementia, anxiety, and depression (Osborne and Hamon 1988). Although the majority of research aimed at understanding 5-HT function, release, uptake, and metabolism has focused on the CNS, an estimated 95% of the 5-HT in the human body is located in the PNS of the gastrointestinal tract, the enteric nervous system (ENS) (Kim and Camilleri 2000). 5-HT fulfills all criteria necessary for classification as a neurotransmitter in the ENS (Gershon 2004) and has been linked to a number of gastrointestinal disorders including irritable bowel syndrome, functional dyspepsia, non-cardiac chest pain, and gastric ulcer formation (Orlicz-Szczesna et al. 1989;Dhasmana et al. 1993). Thus, it is important to consider 5-HT metabolism in both the ENS and CNS. Understanding the catabolic pathways, the enzymes involved and the products of these conversions is particularly important because catabolism is vital to the regulation of 5-HT levels. Elucidating 5-HT catabolic pathways (Fig. 1) may provide novel approaches for the regulation of this compound and thus, improved targets for...
