Lithium Delays Biochemical Circadian Rhythms in Rats

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Abstract
Recent evidence has indicated that a fast circadian oscillator or pacemaker might contribute to affective illnesses, particularly manic depressive disease in humans. To test the hypothesis that Li exerts its therapeutic effect by slowing or delaying overly fast circadian rhythms, 95 rats were fed a Li-containing diet for a period of 3-4 wk, and 91 rats were fed a control diet. The animals were sacrificed at times around the clock. Eight of the 11 substances measured (plasma prolactin, parathyroid hormone, corticosterone and aldosterone, serum Ca and Mg, and cerebellar Ca and Mg) showed large delays in their circadian rhythms in the Li-fed rats. This supports the hypothesis that Li/therapeutic action is to delay overly fast circadian rhythms.