Lithium promotes entrainment of rats to long circadian light-dark cycles.

Manic-depressive patients may have an endogenous circadian oscillator (about 24-hour clock) which runs too fast or which seeks too advanced or early a phase. Lithium salts are a major treatment for manic-depressives and may work by slowing this overly fast clock. Previous experiments with blinded rats demonstrated that lithium could delay free-running circadian rhythms. In this experiment, male rats were exposed to 27- and 28-hour light-dark cycles which were too long to synchronize the rhythms of control animals. In these control animals, the interaction of a faster (about 24-hour) internal rhythm with a slower light-dark cycle produced a beating interaction. cyclic variations in activity were observed as a result. Measurement of wheel-running activity indicated that its circadian rhythm was significantly slowed in lithium-fed animals and became synchronized with the light-dark cycle. This illustrates and supports the hypothesis that an action of lithium may be to delay and resynchronize overly fast circadian rhythms.