2013 Theses Bachelor's

Lithium changes the way light resets the brain’s internal clock in a mouse model of bipolar depression

Liew, Valecia

Lithium is the drug of choice for treating patients suffering from bipolar disorder (BP), a disorder characterized by mood swings between mania and depression. Though the exact pathway by which lithium acts to counteract the symptoms of BP is unknown, we do know that lithium helps animals entrain to a longer circadian rhythm. Studies have shown that patients with BP tend to have a shorter circadian rhythm than the near 24h period shown by a normal individual and experience difficulty synchronizing to the external light and dark (LD) cues of a 24h day. We hypothesize that because light is such a potent entraining cue, lithium may interact with LD signals on the brain’s internal clock, the suprachiasmatic nucleus (SCN), to enable BP individuals entrain to the 24 hour day. In order to determine the effects of lithium on brain and locomotor behavior, mice were placed in a 28 hour day consisting of 14:14 light:dark cycle. Animals were randomly divided into groups and fed either control chow or lithium supplemented chow. Analysis of wheel running behavior and levels of FOS expression in the SCN showed that animals on a lithium diet exhibited a greater response to the light pulse given in the night and were better able to entrain to the longer 28 hour day. We conclude that lithium acts upon an animal’s endogenous clock, thereby facilitating entrainment to a lengthened external cycle.