5-hydroxytryptophan-induced myoclonus: Increased sensitivity to serotonin after intracranial 5,7-dihydroxytryptamine in the adult rat

Abstract

Systemic administration of the serotonin precursor, 5-hydroxytryptophan, produced tremor and myoclonus in rats previously treated with intracisternal injections of 5,7-dihydroxytryptamine and systemic desmethylimipramine, but not in their controls. The behavioural syndrome developed to a maximum at 10–14 days, and persisted at least 16 weeks following intracisternal 5,7-dihydroxytryptamine. The myoclonic syndrome was potentiated by pargyline, but was blocked by d-lysergic acid diethylamide, 2-bromolysergic acid diethylamide, methysergide, and centrally active high doses of the decarboxylase inhibitor, Ro4-4602. Drugs that increase or decrease the effects of other proposed central nervous system neurotransmitters (dopamine, norepinephrine, acetylcholine, and γ-aminobutyric acid) neither reproduced the syndrome nor altered the myoclonus following 5-hydroxytryptophan. Thus, myoclonus induced by 5-hydroxytryptophan following treatment with 5,7-dihydroxytryptamine + desmethylimipramine appears to be specifically related to central indoleamine neurones and may reflect pre- or postsynaptically mediated supersensitivity to serotonin. This animal behavioural syndrome may be relevant to some forms of clinical myoclonus, and should be useful in testing agents that act as agonists or antagonists at serotonin receptors in the central nervous system.