History And Discovery

Serotonin (5-HT) is an indoleamine with wide distribution in plants, animals, and humans. Pioneering histochemistry by Falck et al. (1962) found that 5-HT was localized within specific neuronal pathways and cell bodies. These originate principally from two discrete nuclei, the medial and dorsal raphe. Across animal species, 5-HT innervation is widespread. Although regional variations exist, several limbic structures manifest especially high levels of 5-HT (A. H. Amin et al. 1954).

However, 5-HT levels in the central nervous system (CNS) represent only a small fraction of 5-HT found in the body (Bradley 1989). Because 5-HT does not cross the blood-brain barrier, it must be synthesized locally. 5-HT is released into the synapse from the cytoplasmic and vesicular reservoirs (Elks et al. 1979). Following release, 5-HT is principally inactivated by reuptake into nerve terminals through a sodium/potassium (Na+/K+) adenosine triphosphatase (ATPase)-dependent carrier (Shaskan and Snyder 1970). The transmitter is subsequently subject to either degradation by monoamine oxidase (MAO) or vesicular restorage. Abnormalities in central 5-HT function have been hypothesized to underlie disturbances in mood, anxiety, satiety, cognition, aggression, and sexual drives, to highlight a few. As described by Fuller (1985), there are several loci at which therapeutic drugs might alter 5-HT neurotransmission (Figure 13-1). The explosion of knowledge regarding the serotonergic system can largely be traced to the development of compounds, such as fluoxetine, that block the reuptake of this neurotransmitter.

FIGURE 13-1. Serotonin (5-HT) neuron showing the main steps in the life cycle of 5-HT and the sites at which drugs act.

Somatodendritic autoreceptor

Somatodendritic autoreceptor

cr-Methyl 5-HTP

5-HTP decarboxylase

Prevent 5-HT storage

Reserpine Tetra benazine

5-HT releasers p-Chlorophenylalanine Fenfluramine

Terminal auto receptor

Postsynaptic receptor

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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