Serotonin Kompakt – Teil 1

Abstract

As soon as in the 1960's, the role of serotonin (5-Hydroxytryptamin, 5-HT) in psychiatric disorders was realized, which was further substantiated by several lines of evidence amounting to a huge body of knowledge. The indolamine 5-HT belongs to the class of monoamine transmitters and can be found in the serotonergic neurons of the raphe nuclei in the brain stem. In the periphery, it is mainly present in the gastrointestinal system and the pineal gland. 5-HT is implicated in a variety of cognitive, emotional and vegetative behaviors, as well as in the regulation of circadian rhythms. Apart from its role as a neurotransmitter, it has an important function in prenatal development, where its expression pattern is tightly regulated, and in adult neurogenesis. The numerous effects of 5-HT are mediated by specific pre- and postsynaptic receptors, whose localization and functions are further described here. The serotonin transporter (SERT), which accomplishes the re-uptake of 5-HT into the neuron following its release in the synaptic cleft, not only has an important role in the termination of serotonergic neurotransmission but is also an important drug target for antidepressant compounds. In this part of the review, the neurobiological underpinnings of 5-HT synthesis, metabolism, and neurotransmission as well as the corresponding physiological consequences are summarized, while in the second part, an overview on clinical findings is provided and critically discussed.

Serotonergic Modulation of Conditioned Fear

“…Upon fusion of the vesicle with the cell membrane, 5-HT is released into the synaptic cleft, where it can diffuse and bind to receptors to one or more of the 16 5-HT receptors that have been identified in the mammalian brain: 5-HT 1A,1B,1C,1D,1E,1F , 5-HT 2A,2B,2C , 5-HT 3A,3B , 5-HT 4 , 5-HT 5A,5B , 5-HT 6 , and 5-HT 7 . All of them are G-protein coupled receptors, except for the 5-HT 3A,3B receptors, which are ligand-gated ion channel receptors [24, 25]. In rodents, the presynaptic 5-HT 1B receptor autoregulates 5-HT release, while in humans it is the 5-HT 1D receptor that fulfils this purpose [25].…”

“…All of them are G-protein coupled receptors, except for the 5-HT 3A,3B receptors, which are ligand-gated ion channel receptors [24, 25]. In rodents, the presynaptic 5-HT 1B receptor autoregulates 5-HT release, while in humans it is the 5-HT 1D receptor that fulfils this purpose [25]. The presynaptic 5-HT 1A receptor is located in the raphe nuclei and regulates the firing of serotonergic raphe neurons that project to widespread regions in the brain as well as to the spinal cord.…”

Serotonergic innervation and serotonin receptor expression of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei

“…Serotonergic neurotransmission is implicated in various functions in the central nervous system, ranging from the regulation of food intake, body temperature and biorhythms to influencing attention, motivation and other cognition (Kriegebaum et al 2010). One of its most relevant functions, from a psychiatric and social point of view, is its impact on emotional states like anxiety and associated psychiatric diseases.…”

Pharmacology of serotonin and female sexual behavior

“…5-HT 1B receptors are the most prominent such terminal autoreceptors in rats while, in humans, 5-HT 1D receptors are the dominant such receptor (Kriegebaum et al, 2010; Kroeze et al, 2012). Both 5-HT 1B and 5-HT 1D receptors may be located on neuronal terminals and have similar, though not identical, pharmacology (Hannon and Hoyer, 2008; Kroeze et al, 2012).…”