Axons serotonin release

The anatomic sites of noradrenergic control of serotonin release are shown in Figure 5—47, and include the brake at the axon terminals in the cortex and the accelerator at the cell bodies in the brainstem. This is shown schematically in Figure 5-48. 

FIGURE 5—47. Two types of norepinephrine interaction with serotonin are shown here. In the brainstem, a pathway from locus coeruleus to raphe interacts with serotonergic cell bodies there and accelerates serotonin release. A second noradrenergic pathway to target areas in the cortex also interacts with serotonin axon terminals there and brakes serotonin release. 

Once the 5HT1A somatodendritic autoreceptors are desensitized, 5HT can no longer effectively inhibit its own release, and the serotonin neuron is therefore dis-inhibited. This results in a flurry of >HT release from axons due to an increase in neuronal impulse flow (Fig. 6—38). This is just another way of saying that the serotonin release is turned on at the axon terminals. The serotonin that now pours out of the various projections of serotonin pathways in the brain theoretically mediates the various therapeutic actions of the SSRls. 

Neurotransmitten Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic deft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic add, substance P, enkephalins, endorphins, and serotonin. [EU]... 

The neurochemical basis for these effects has also heen studied in some detail. Researchers have learned that MDMA (and its phenyl-ethylamine cousins) interferes with the normal function of at least two neurotransmitters in the brain, serotonin and dopamine. Under normal circumstances, nerve messages are transmitted through the CNS when an axon on one neuron releases a neurotransmitter, such as serotonin or dopamine, which travels across the synapse between two neurons and is taken up at a receptor site in the second neuron. 

Since the main clinical use for antisympathotonics is in the treatment of essential hypertension, such drugs will be discussed in Chapter 20 in more detail. The alkaloid reserpine from Rauwolfia serpentina was the first drug used clinically to reduce sympathetic tone. Reserpine reduce the ability of storage and release of various transmitters (adrenaline, noradrenaline, serotonine and dopamine) by an irreversible destruction of the axonal vesicle membranes. The duration of the reserpine effect is actually determined by the de novo synthesis of these structure. Beside various central side effects like sedation, depression, lassitude and nightmares the pattern of unwanted effects of reserpine is determined by the shift of the autonomic balance towards the parasympathetic branch myosis, congested nostrils, an altered saliva production, increased gastric acid production, bardycardia and diarrhea. As a consequence of the inhibition of central dopamine release, reserpine infrequently shows Parkinson-like disturbances of the extrapyramidal system. 

FIGURE 6-39. Mechanism of action of serotonin selective reuptake inhibitors (SSRIs)—part 5. Finally, once the SSRIs have blocked the reuptake pump (Fig. 6-36), increased somatodendritic serotonin (Fig. 6-36), desensitized somatodendritic serotonin 1A autoreceptors (Fig. 6—37), turned on neuronal impulse flow (Fig. 6-38), and increased release of serotonin from axon terminals (Fig. 6— 38), the final step shown here may be the desensitization of postsynaptic serotonin receptors. This has also been shown in previous figures demonstrating the actions of monoamine oxidase (MAO) inhibitors (Fig. 6-4) and the actions of tricyclic antidepressants (Fig. 6—6). This desensitization may mediate the reduction of side effects of SSRIs as tolerance develops. 

Serotonin has important influences on dopamine, but that influence is quite different in each of the four dopamine pathways. Understanding the differential serotonergic control of dopamine release in each of these four pathways is critical to understanding the differential actions of antipsychotic drugs that block only dopamine 2 receptors (i.e., the conventional antipsychotics) versus antipsychotic drugs that block both serotonin 2A and dopamine 2 receptors (i.e., the atypical antipsychotics). That is, serotonin inhibits dopamine release from dopaminergic axon terminals in the various dopamine pathways, but the degree of control differs from one dopamine pathway to another. 

FIGURE 11—17. Serotonin-dopamine interactions in the nigrostriatal dopamine pathway. Serotonin inhibits dopamine release, both at the level of dopamine cell bodies in the brainstem substantia nigra and at the level of the axon terminals in the basal ganglia—neostriatum (see also Figs. 11 — 18 through 11 —20). In both cases, the release of serotonin acts as a brake on dopamine release. 

FIGURE 11 — 18. Serotonin regulation of dopamine release from nigrostriatal dopamine neurons, part 1. Here, dopamine is being freely released from its axon terminal in the striatum because there is no serotonin causing any inhibition of dopamine release. 

Histamine H3-receptors have been reported to regulate not only the release and turnover of histamine via autoreceptors on histaminerglc nerve endings [1-3], but also the releases of noradrenaline, dopamine, serotonin, and acetylcholine via heteroreceptors on non-histaminerglc axon terminals [22-26], Thioperamide increased the release of these neurotransmitters, while... 

THE POWER OF A FEW PERCENT Neurons that produce and release serotonin in the brain are organized into a series of nuclei that lie in a chain along the midline, or seam, of the brainstem these are called the raphe nuclei (raphe means seam in Latin). These neurons project their axons to every part of the brain, and some of these axons make contact with blood vessels the neurons also project downward into the spinal cord. If you were able to insert a recording device into the major raphe nuclei and listen to the activity of your serotonin neurons, you would discover that they have a regular slow spontaneous level of activity that varies little while you are awake. When you fall asleep, the activity of these neurons slows. When you start to dream—or if, as we ll see shortly, you ingest a hallucinogen—these neurons cease their activity completely. 

Our knowledge of presynaptic dopamine and serotonin receptors dates back to the 1970s (Famebo and Hamberger 1971). Presynaptic histamine receptors were discovered in 1983 (Arrang et al. 1983). Presynaptic dopamine receptors occur as autoreceptors, i.e., on dopaminergic axon terminals, and as heteroreceptors on nondopaminergic axon terminals. By analogy the same holds true for presynaptic histamine and serotonin receptors. The early days of the dopamine autoreceptors were stormy, but the controversies were finally solved (see Starke et al. 1989). The main function that presynaptic receptors affect is transmitter release, which in this article means Ca2+-dependent exocytosis. However, some receptors discussed in... 

If presynaptic histamine receptors are more uniform than presynaptic dopamine receptors, the contrary holds true for presynaptic serotonin receptors they are even more diverse than presynaptic dopamine receptors. As mentioned in the Introduction, presynaptic 5-HT3 receptors, being ligand-gated ion channels, are covered in the chapter by Dorostkar and Boehm and will be mentioned here only occasionally. Presynaptic G protein-coupled 5-HT receptors inhibit the release of serotonin from serotonergic axon terminals and inhibit or enhance the release of other neurotransmitters (Table 4). 

Presynaptic receptor that is activated by a neurotransmitter from an adjacent neuron the type of neurotransmitter activating the heteroceptor differs from that released from the axon. 5-Hydroxyindoleacetic acid, the main metabolite of 5-hydroxytryptamine (serotonin) formed by monoamine oxidase. 

Skeletal muscles are controlled by large nerves in the spinal cord. The nerve cell or neuron is part of the spinal cord, but its projections, the axon and the many dendrites course outward to connect to muscle cells. The nerve axon is a sensory device that senses the muscle cells current condition. The dendrites are motor fibers that deliver the instructions to change its state to the muscle fiber. The area at which the muscle and nerve connect is called the neuromuscular junction. It is here that the end releases a chemical called a neurotransmit-ter that crosses the microscopic space between the nerve and muscle and causes the desired response. Five such neurotransmitters have been described acetylcholine, serotonin, norepinephrine, glycine, and gamma-ammi-nobutyric acid or GABA. Of these, the functions of three are known. Acetylcholine excites muscle activity and glycine and GABA inhibit it. 

---