Central nervous system serotonin

Enterochromaffin cells are interspersed with mucosal cells mainly in the stomach and small intestine. In the blood, serotonin is present at high concentrations in platelets, which take up serotonin from the plasma by an active transport process. Serotonin is released on platelet activation. In the central nervous system, serotonin serves as a transmitter. The main serotonin-containing neurons are those clustered in form of the Raphe nuclei. Serotonin exerts its biological effects through the activation of specific receptors. Most of them are G-protein coupled receptors (GPCRs) and belong to the 5-HTr, 5-HT2-, 5-HT4-, 5-HTs-, 5-HT6-, 5-HT7-receptor subfamilies. The 5-HT3-receptor is a ligand-operated ion channel. 

Venlafaxine (Effexor, Wyeth) Central nervous system Serotonin-norepinephrine reuptake inhibitor... 

Serotonin, also called 5-hydroxytryptamine, is synthesized and stored at several sites in the body (Figure 21.18). By far the largest amount of serotonin is found in cells of the intestinal mucosa. Smaller amounts occur in platelets and in the central nervous system. Serotonin is synthesized from tryptophan, which is hydroxy-lated in a reaction analogous to that catalyzed by phenylalanine hydroxylase. The product, 5-hydroxytryptophan, is decarboxylated to serotonin. Serotonin has multiple physiologic roles, including pain perception, affective disorders, and regulation of sleep, temperature, and blood pressure. 

The involvement of the central nervous system serotonin function in the pathogenesis and treatment of affective disorders has been a subject of intensive research during the past 30 years.33 36 Studies using serotonin precursors and agonists as pharmacologic probes and measurements of cerebrospinal fluid monoamine metabolite levels indicated that alterations in central nervous system serotonin function may be involved in the pathophysiology of depression. Since the synthesis of serotonin depends on dietary intake of the precursor tryptophan, many studies have utilized tryptophan depletion techniques by which patients were fed a tryptophan-free diet for various time intervals. 

A number of reviews have described the important role that serotonin, a derivative of tryptophan, plays within the central nervous system.22-24 Also, Chapter 7 reviewed the importance of serotonin in selected diseases of the central nervous system. Serotonin neurons participate in a wide range of behaviors, including sleep, feeding, aggression, locomotor activity, and pain sensitivity.25 Dietary manipulations that alter brain tryptophan levels can, in animals and in humans, affect many of these behaviors. Several examples of these effects are cited. 

Nierenberg DW, SemprebonM. The central nervous system serotonin s3mdrome. ClinPhar-macolTher 993) 53, 84-8. 

Nierenberg DW, SemprebonM The central nervous system serotonin syndrome. Clin Pharmacol Ther (1993) 53,84-8. 

There is also evidence for ATP as a cotransmitter with y-aminobutyric acid or with glutamate, serotonin, NA or dopamine in nerves in the central nervous system. 

TK NKxr displays a broad distribution in both peripheral tissues and in the central nervous system (CNS). In both CNS and enteric neurons, NKxr stimulation increase their excitability, whereas in trigeminal ganglion neurons SP has no intrinsic electrophysio-logical effects but is capable to enhance the amplitude of the inward current induced by the stimulation of serotonin 5-HT3 recqrtors. This enhancement dqjends on the activation of PKC via the stimulation of NKX recqrtors. This is an interesting case of receptor cross talk. Other functions of NKxr have been also highlighted. 

The various stimulants have no obvious chemical relationships and do not share primary neurochemical effects, despite their similar behavioral effects. Cocaines chemical strucmre does not resemble that of caffeine, nicotine, or amphetamine. Cocaine binds to the dopamine reuptake transporter in the central nervous system, effectively inhibiting dopamine reuptake. It has similar effects on the transporters that mediate norepinephrine and serotonin reuptake. As discussed later in this chapter in the section on neurochemical actions mediating stimulant reward, dopamine is very important in the reward system of the brain the increase of dopamine associated with use of cocaine probably accounts for the high dependence potential of the drug. 

Tryptamine itself is found in all major centers of the brain. Its physiologic role in central nervous system (CNS) function, however, remains unclear. 5-Hydroxytryptamine (5-HT, serotonin) is an important neurotransmitter in the CNS. The structural similarity of the tryptamine-related hallucinogens with 5-HT presumably forms the neurochemical basis for their action within the CNS. 

Steinbusch, H.W.M. Distribution of serotonin-immunoreactivity in the central nervous system of the rat—Cell bodies and terminals. 

Steinbusch, H.W.M. Verhofstad, A.A.J. and Joosten, H.W.J. Localization of serotonin in the central nervous system by immunohistochemistry Description of a specific and sensitive technique and some applications. Neuroscience 3 811-819, 1978. 

Benkirane, S. Arbilla, S. and hanger, S.Z. A functional response to D1 dopamine receptor stimulation in the central nervous system Inhibition of the release of [ H]-serotonin from the rat substantia nigra. Naunyn-Schmiedebergs Arch Pharmacol 335 502-507, 1987. 

Enteric nerves control intestinal smooth muscle action and are connected to the brain by the autonomic nervous system. IBS is thought to result from dysregulation of this brain-gut axis. The enteric nervous system is composed of two gan-glionated plexuses that control gut innervation the submucous plexus (Meissner s plexus) and the myenteric plexus (Auerbach s plexus). The enteric nervous system and the central nervous system (CNS) are interconnected and interdependent. A number of neurochemicals mediate their function, including serotonin (5-hydroxytryptamine or 5-HT), acetylcholine, substance P, and nitric oxide, among others. 

Complicated processes govern wakefulness, sleep, and the transitions leading to sleep initiation and maintenance. Although the neurophysiology of sleep is complex, certain neurotransmitters promote sleep and wakefulness in different areas of the central nervous system (CNS). Serotonin is thought to control non-REM sleep, whereas cholinergic and adrenergic transmitters mediate REM sleep. Dopamine, norepinephrine, hypocretin, substance P, and histamine all play a role in wakefulness. Perturbations of various neurotransmitters are responsible for some sleep disorders and explain why various treatment modalities are beneficial. 

SSRIs are theorized to reduce the frequency of hot flashes by increasing serotonin in the central nervous system and by decreasing LH. Of the SSRIs, citalopram, paroxetine, and sertraline all have been studied and have demonstrated a reduction in hot flashes while treating other symptomatic complaints such as depression and anxiety.33 Venlafaxine, which blocks the reuptake of serotonin and norepinephrine, has demonstrated a reduction in hot flashes primarily in the oncology population.34 Overall, these antidepressant medications offer a reasonable option for women who are unwilling or cannot take hormonal therapies, particularly those who suffer from depression or anxiety. These agents should be prescribed at the lowest effective dose to treat symptoms and may be titrated based on individual response. 

Synergy of unwanted pharmacological effect ginseng and its products will inhibit the central nervous system (CNS) when they are applied with luminal, chloral hydrate, or ephedrine, which can increase the release of dopamine, noradrenaline, and serotonin in the CNS thus inducing a hypertensive crisis if monoamine oxidase inhibitors (MAOIs) are given simultaneously. 

Hydroxy tryptamine, or serotonin, is a neurotransmitter in the central nervous system (CNS). The nerve-cell bodies of the major serotoninergic neurones are in the midline raphe nuclei of the rostral pons, and ascending fibers innervate the basal ganglia, hypothalamus, thalamus, hippocampus, limbic forebrain, and areas of the cerebral cortex. The serotoninergic system plays an important role in the control of mood and behavior, motor activity, hunger, thermoregulation, sleep, certain hallucinatory states, and some neuro-endocrine mechanisms. 

Chan-Palay, V., Jonsson, G., Palay, S. L. (1978). Serotonin and substance P coexist in neurons of the rat s central nervous system. Proc. Natl. Acad. Sci. USA 75, 1582-6. 

Cornea-Hebert, V., Riad, M., Wu, C., Singh, S. K. Descarries, L. (1999). Cellular and subcellular distribution of the serotonin 5-UT2A receptor in the central nervous system of adult rat. J. Comp. Neurol. 409, 187-209. 

Rothman, R.B., Baumann, M.H., Dersch, C.M. et al. Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse. 39 32, 2001. 

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