Serotonergic nerve

The raphe nuclei are a cluster of nuclei found in the brainstem, where they are located in the medial portion of the formatio reticularis, the raphe. (The raphe is the junction of the left and right brainstem hemisphere, hence the name raphe=seam). Serotonergic nerve cells in the CNS originate from the raphe nuclei, i.e., their rostral portion, and because of their wide-ranging projections appear to supply serotonin (5HT) to the rest of the brain. 

A related strategy would be to inactivate the 5-HTib/id autoreceptors which are found on serotonergic nerve terminals and so prevent feedback inhibition of 5-HT release in the terminal field. These drugs would not prevent the impact of indirect activation of 5-HTia receptors, and the reduced neuronal firing, by SSRIs (described above), but they would augment 5-HT release in the terminal field once the presynaptic 5-HTia receptors have desensitised. Selective 5-HTib/id antagonists have been developed only recently but will doubtless soon be tested in humans. 

The results of the studies reviewed here show that the neurotoxic effects of MDMA generalize to the primate. Further, they indicate that monkeys are considerably more sensitive than rats to the serotonin-depleting effects of MDMA, and that the dose-response curve of MDMA in the monkey is much steeper than in the rat. Perhaps as a consequence of this, the toxic effects of MDMA in the monkey involve serotonergic nerve fibers as well as cell bodies, whereas in the rat, only nerve fibers are affected. The present studies also show that the toxic dose of MDMA in the monkey... 

Commins et al. (1987) have also reported the formation of 5,6-dihydroxy-tryptamine in rat hippocampus after a single, high doses of methamphetamine. They suggested that the formahon of 5,6-dihydroxytryptamine, a known neurotoxie substance, may mediate the neurotoxie effects of methamphetamine toward serotonergic nerve terminals. 

Kalia, M., O Callaghan, J.R, Miller, D.B., and Kramer, M., Comparative study of fluoxetine, sibutra-mine, sertraline and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry, Brain Res. 858(1), 92-105, 2000. 

Trulson, M. E., Eubanks, E. E., and Jacobs, B. L. (1976) Behavioral evidence for supersensitivity following destruction of central serotonergic nerve terminals by 5,7-dihydroxytryptamine. J. Pharmacol. Exp. Ther., 198 23. 

MDMA and MDA produce serotonergic nerve damage in rats, but not when injected directly into the brain. HLMs make two glutathione regioisomers from MDA, both of which depend on CYP2D activity. The 5-(glutathion-S-yl)-alpha-MeDA adduct is behaviorally active in the rat (Easton et al., 2003). 

HT is synthesized in serotonergic nerve terminals from tryptophan in a series of reactions catalyzed by tryptophan hydroxylase and L-aromatic acid decarboxylase,... 

Not only is methamphetamine administration toxic to the dopaminergic system, but the serotonergic system in the various brain areas is also altered. Hotchkiss and Gibb (1980) reported that methamphetamine, administered as described above, decreased tryptophan hydroxylase (TPH) activity in the serotonergic nerve terminal of rat brain and spinal cord. Similarly, the content of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were also severely depressed. In contrast to the effects in the dopaminergic system, these serotonergic parameters were decreased by methamphetamine within 15 minutes after a single dose... 

Methamphetamine, when administered in large doses, causes neurochemical deficits in both the dopaminergic and serotonergic nerve terminals of the brain that persist for extended periods of time. 

DA or a toxic DA metabolite might contribute to the degeneration of both dopaminergic and serotonergic nerve terminals and,... 

The intrinsic primary afferent neurons are present in both the myenteric and submucosal plexuses. They respond to luminal chemical stimuli, to mechanical deformation of the mucosa, and to stretch. The nerve endings of the primary afferent neurons can be activated by endogenous substances (e.g., serotonin) arising from local enterochromaffin cells or possibly from serotonergic nerves. 

This neurotoxin produced permanent destruction to serotonergic nerve endings and fibers. 

Hence, these studies in guinea pig suggest that, in addition to their presynaptic location on serotonergic nerve terminals where they act as 5-HT autoreceptors... 

HT occupies an important position because of its du2d. localization in serotonergic nerves and pineal parenchyma and because of ll t regulation of its metabolism, which leads to the formation of S-H and 5-MeO-tryptophols and 5-H and 5-MeO indoleacetlc acids. Cyclic derivatives of the carbolin (5-MeO-TOL) type may also be derived from these compounds. 

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