5-HT-mediated myoclonus in the guinea pig as a model of brainstem 5-HT and tryptamine receptor action.
Indoleamine-induced myoclonus in guinea pigs is a specific model of brainstem 5-HT function that can be used to characterize the indoleamine systems initiating myoclonus. 5-HT precursors and indole-containing 5-HT agonists induce myoclonus in guinea pigs, but piperazine-containing compounds do not. This selectivity of action correlates with the ability of 5-HT agonists to act at 5-HT-1 receptors. Further evidence for the involvement of a brainstem 5-HT receptor subpopulation in the initiation of myoclonus is shown by the differential ability of 5-HT antagonists to inhibit 5-HTP-induced myoclonus and of 5-HT reuptake blockers to potentiate threshold myoclonus. Distinct tryptamine receptors also may be involved in producing myoclonus, since indoleamine antagonists show differing potencies in inhibiting 5-HTP- and tryptamine-induced myoclonus. Tryptamine-induced myoclonus is, however, dependent on intact presynaptic 5-HT function. Biochemical studies indicate that 5-HT is primarily responsible for 5-HTP-evoked myoclonus, whereas tryptamine predominates in tryptamine-induced myoclonus. Both 5-HT and tryptamine may contribute to myoclonus produced by L-tryptophan. Indoleamine-induced myoclonus in guinea pigs may be valuable in studying the organization of brainstem indoleamine systems that may be involved in some forms of human myoclonus.
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Luscombe
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Jenner
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Marsden
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002230:Carbidopa / Q000494:pharmacology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007211:Indoles / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D009207:Myoclonus / Q000503:physiopathology*; D010293:Pargyline / Q000494:pharmacology; D000077489:Piperazine; D010879:Piperazines / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology; D014364:Tryptophan / Q000494:pharmacology
D007211:Indoles; D008996:Monoamine Oxidase Inhibitors; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D014363:Tryptamines; D000077489:Piperazine; D012701:Serotonin; C030820:tryptamine; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D010293:Pargyline; D006916:5-Hydroxytryptophan; D002230:Carbidopa