Some antidepressant agents (Li+, monoamine oxidase type A inhibitors) perturb the ultradian clock in Saccharomyces cerevisiae

摘要

A continuous culture of Saccharomyces cerevisiae shows continuous autonomous oscillatory behaviour: this system is controlled by an ultradian clock. We used the most convenient observable (dissolved 02) to assess the effects of various psychotropic agents on the period (tau) and waveform of the oscillation. The threshold for a measurable perturbation by LiCl was between 10muM and 100muM; the value of iota was increased from the normal 40 min to 50 min. Higher concentrations (up to 800muM), gave a dose-dependent period lengthening response to 68 min. At higher doses, the oscillation showed an abrupt transition to a state of higher complexity, where tau drop 5 h. Recovery was also dose-dependent; this took 8 h at 100muM or 36 h at 600muM: at 1.2mM Li+ organisms never recovered to a stable oscillatory state. Very high concentrations of inhibitors of monoamine oxidase type A + B (Phenelzine) or type A (Iproniazid) led to immediate period lengthening. The type B inhibitor (Pargyline) gave no detectable effect. Melatonin (1.5mM), serotonin (1.5mM) dopamine (5 mM) or tyramine (2.5 mM) were also without effect. The addition of glutamate perturbed the oscillation but did not cause a transient period lengthening. [References: 38]