Serotonergic nerve terminal

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. 

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. 

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,... 

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 neurons originate in the raphe nudei in the midline region of the pons and upper brain stem. There are several serotonergic pathways in the CNS that innervate a variety of lower (e.g. medulla and spinal cord) and higher CNS centres such as cerebellum, thalamus, neocortex and the limbic system. Serotonergic nerve terminals are able to synthesise their own 5-HT from L-tryptophan, an ability they share with enterochromaffin cells. Neuronal reuptake and vesicular storage protects 5-HT from deamination by MAO. 

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