Lithium delays biochemical circadian rhythms in rats

Recent evidence has indicated that a fast circadian oscillator or pacemaker might contribute to affective illnesses, particularly manic depressive disease. In order to test the hypothesis that lithium exerts its therapeutic effect by slowing or delaying overly fast circadian rhythms, 95 rats were fed a lithium-containing diet for a period of 3-4 weeks, and 91 rats were fed a control diet. The animals were sacrificed at times around the clock. Eight of the eleven substances measured (plasma prolactin, PTH, corticosterone, and aldosterone, serum calcium and magnesium, and cerebellar calcium and magnesium) showed large delays in their circadian rhythms in the lithium-fed rats. This supports the hypothesis that lithium's therapeutic action is to delay overly fast circadian rhythms.