Brain raphe system

S-HT occurs in the central nervous system of all vertebrates and seems to be concentrated in the phylogenetically older parts of the brain connected with the autonomic nervous system and the reticular formation (Table 2). The use of histofluorescence techniques has made it possible to confirm the finding of uneven regional S-HT distribution based on chemical and biochemical assays. S-HT neurons have now been visualized (Fig. 7 and Fig. 10 in Sect B, Chap. S.2). Most S-HT neurons seem to be located in the nuclei of the raphe system and their axons travel towards several parts of the brain and the spinal cord. These axons are particularly concentrated in the medial forebrain bundle (MFB) (Fig. 7X which can be selectively destroyed, leading to a significant decrease in S-HT in some areas of the brain. Diurnal and seasonal variations in S-HT levels in several areas of the brain have been demonstrated. 

DAT is predominantly expressed by dopaminergic brain neurons, NET by noradrenergic neurons in the central and peripheral nervous system, and SERT is restricted to the axons of serotonergic neurons, which originate in the raphe nuclei and innervate numerous higher brain regions therefore SERT is widely distributed in the brain. Outside the brain, 5HT transport can be measured on non-neuronal cells (e.g. platelets, lympho-blastoid cells and smooth muscle cells) most of the 5HT appearing in the circulation is taken up by platelets. 

These differences may be extremely important in understanding the role of these two distinct serotonergic systems, arising from the dorsal and median raphe nuclei, in normal brain function and in mental illness. 

The detection of serotonin in nervous and non-nervous tissue was aided by the development of the Falck-Hillarp histochemical technique, a method whereby freeze-dried sections of tissue, when exposed to formaldehyde vapour cause indoleamines to emit a yellow fluorescence. Dahlstrom and Fuxe used this technique to show that the highest concentration of serotonin in the brain is located in the raphe nuclei, projections from these cell bodies ascending to the forebrain via the medial forebrain bundle. Descending fibres were also shown to project to the dorsal and lateral horns and the intermediolateral column of the spinal cord. Detailed observation of the distribution of the serotonergic system in the brain became possible with... 

Figure 5. Serotonergic systems in the human brain with projections to the cerebral cortex from the dorsal raphe nucleus (continuous line) and from the median raph nucleus (dotted line). Projections from more posterior nuclei also as continuous lines.

DahlstrOm A, Fuxe K (1964) Evidence for the existence of monoamine-containing neurons in the central nervous system. Acta Physiol Scand 62 2-55 Daugherty WP, Corley KC, Phan TH, Boadle-Biber MC (2001) Further studies on the activation of rat median raphe serotonergic neurons by inescapable sound stress. Brain Res 923 103-111... 

Kirby LG, Chou-Green JM, Davis K, Lucki I (1997) The effects of different stressors on extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. Brain Res 760 218-230 Kirby LG, Rice KC, Valentino RJ (2000) Effects of corticotropin-releasing factor on neuronal activity in the serotonergic dorsal raphe nucleus. Neuropsychopharmacology 22 148-162 Kozicz T, Yanaihara H, Arimura A (1998) Distribution of urocortin-like immunoreactivity in the central nervous system of the rat. J Comp Neurol 391 1-10 Lavicky J, Dunn AJ (1993) Corticotropin-releasing factor stimulates catecholamine release in hypothalamus and prefrontal cortex in freely moving rats as assessedby microdialysis. J Neurochem 60 602-612... 

Most of the serotonin in the brain is in the brainstem, specifically in the raphe nuclei considerable amounts also are present in areas of the hypothalamus, the limbic system, and the pituitary gland. Current evidence indicates that serotonin is involved in the regulation of several aspects of behavior, including sleep, pain perception, depression, sexual activity, and aggressiveness. Some of the most important antidepressant agents are believed to prevent the reuptake of serotonin (see Chapter 33). Serotonin also may be involved in temperature regulation and in the hypothalamic control of the release of pituitary hormones. 

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