Lisuride and LSD: Dopaminergic and serotonergic interactions in the "serotonin syndrome"

A characteristic behavioral syndrome has been associated with stimulation of central serotonin receptors in rats. This behavior can be produced by inhibition of monoamine oxidase and administration of 5-hydroxytryptophan as well as by direct acting serotonergic agonists. LSD and the novel ergot derivative lisuirde produced this syndrome in rats. These drugs possess both serotonergic and dopaminergic properties. Since changes in dopaminergic function have also been reported to affect the so-called serotonin syndrome, it was not clear how the two ergot drugs acted to produce this syndrome. The syndrome produced by pargyline and 5-hydroxytryptophan methyl ester was blocked by haloperidol, methysergide, parachlorophenylalanine, and alpha-methylparatyrosine; these treatments failed to block the effects of lisuride. Metoclopramide did not block the syndrome produced by either lisuride or pargyline plus 5-hydroxytryptophan methyl ester. Methysergide partially blocked the behavioral effects of LSD; pretreatment with either haloperidol or metoclopramide potentiated and prolonged the behavioral effects of LSD. The results suggest that dopaminergic modulation of the serotonin syndrome occurs before the serotonin receptor involved in this behavior. Also, the differences between LSD and lisuride may be relevant to their different psychopharmacological properties.